On 28 June, James scored both goals to defeat Uruguay 2–0 at the Maracanã in the round of 16, taking Colombia to its first ever World Cup quarter-finals. These goals made him the first player to score in all of his team’s opening matches since Ronaldo and Rivaldo in 2002. His volleyed opening goal was described as “one of the greatest goals the World Cup has ever seen” by opposing manager Óscar Tabárez, who also called James “the best player in the World Cup.” Because of his performance against the Uruguayans, James was named by FIFA as man of the match for the third time in four matches. The volley was later voted as the best goal in the tournament by more than four million people on FIFA’s website and won the FIFA Puskás Award for the best goal of the year. In the quarter-final against Brazil, he scored his sixth goal of the tournament, a penalty in Colombia’s 2–1 defeat.

Born in Cúcuta, Norte de Santander, James spent his childhood in the city of Ibagué, Tolima. He was born to Wilson James Rodríguez Bedoya and Maria Del Pilar Rubio. James started his professional football career in 2006 with the Colombian second division club Envigado, with which he reached the Colombian first division through the 2007 promotion. He became the second youngest Colombian player to start a professional match, playing his first match on 21 May 2006, at the age of 14.

James was part of the Colombia U-17 team that finished runners-up in the 2007 South American Under-17 Championships, where he scored three goals. He also helped Colombia advance to the knockout stages during the 2007 FIFA U-17 World Cup, where they eventually lost to the winners of the tournament Nigeria.

In 2008, he was signed by Argentine team Banfield. He made his first team debut on 7 February 2009, and scored his first goal for the club on 27 February with a long range strike in a 3–1 victory over Rosario Central. He finished his first season with a goal in 11 appearances.

In 2009, he became a regular first-team player, featuring in every game of the Apertura 2009. At just 17, he became the youngest foreigner to score a goal in Argentina. His second goal for Banfield came on 26 September, when he scored with a strike into the top corner from outside of the area in an important 2–1 win against Newell’s Old Boys, a victory that helped Banfield win the Argentine championship for the first time in the club’s history.

In December 2009, Italian club Udinese planned to make a bid for James for a reported €5 million after the 2010 Copa Libertadores. However, Banfield rejected the bid, labelling it as “insufficient”.

For the Clausura 2010, on 13 February 2010, James scored a golazo in the match against archrivals Lanús with a left-footed lob to make the game 2–0 in the final minutes. After the game, daily sports website Diario Olé compared his playing and personal style to Cristiano Ronaldo and nicknamed him the “James Bond of Banfield”.

On 10 February 2010, James scored his first Copa Libertadores goal in a 2–1 home victory over Mexican club Monarcas Morelia. James added to his glowing reputation a week later with a goal in a daunting victory over Copa Libertadores group rivals Deportivo Cuenca away from home, scoring the fourth goal of the game with a nice finish in the area on his left foot. Banfield thrashed the home team 4–1. His wonderful scoring season continued with a brace in the Copa Libertadores group game on 10 March 2010. In an away match against Uruguayan club Nacional, James scored first with a diving header and then from the penalty spot on his right foot. The game ended with a 2–2 draw. The 18-year-old netted another goal against Brazilian club Internacional on 29 April 2010 in the first leg match of Copa Libertadores 2010 Round 16, which Banfield won 3–1. This goal brought his tally to five goals in seven games. However, James’ international season ended in defeat as his team went down on away goals with a 0–2 defeat in Porto Alegre in the second leg, in which James was red carded for two fouls.

On 6 July 2010, James was signed by Porto for €5.1 million, with 30% economic rights retained by other parties. He signed a four-year contract with a €30 million release clause. Porto later re-sold 10% economic rights to third parties. On 18 July, he played his first game and scored his first goal in a friendly against Ajax. In November, Porto sold 35% economic rights (half of 70%) to Gol Football Luxembourg, S.A.R.L. for €2.5 million.

On 15 December 2010, James scored his first competition goal in Europe in a 3–1 home victory against Bulgarian club CSKA Sofia. James scored a hat-trick and assisted once against Vitória de Guimarães in the 2011 Taça de Portugal Final, which Porto won 6–2. On 17 May, Porto bought the remaining 30% economic rights from Convergence Capital Partners B.V. for €2.25 million and once again hold more than half of the economic rights with 55%. On 13 June, James signed a new five-year contract in which the release clause increased to €45 million. In no more than 24 appearances did he score six goals, provide eight assists and play a part in the Europa League victory. He finished the 2010–11 season with six goals in 31 appearances.

In the 2011–12 season, James scored 14 goals for Porto and delivered 11 assists. In 2011, James won the LPFP Award for Breakthrough Player of 2011–12 Primeira Liga season at age 20, becoming the first Colombian player to do so. He is a two-time winner of the SJPF Player of the Month. James won the Portuguese Golden Ball award in 2012, becoming the second Colombian to win the award after Radamel Falcao as well as the youngest player ever to hold the honour. On 20 September 2011 in a league match against Feirense, he punched Rabiola and was subsequently dismissed, missing the match against Benfica.

During the 2011 South American U-20 Championship, he provided three assists. During the 2011 U-20 World Cup, he was named captain of the U20 squad due to his impressive leadership and talent. By scoring three goals and providing three assists in the tournament, he gained international attention as a promising star and made many consider him as a potential key member of the Colombian senior squad.

On 29 September 2011, James received his first call-up to the Colombia senior side for a match against Bolivia on 11 October 2011. He was selected as the man of match due to his incredible performance including the initiation of the goal scored in the last minute by his former Porto teammate Radamel Falcao which gave Colombia a 2–1 win. Under the new manager José Pékerman, he played a crucial part in setting up both goals in a 2–0 victory over Mexico. He scored his first goal for Colombia against Peru. Colombia went on to win the match and boosted its place in the World Cup qualifying table from sixth to fifth.

Prior to the second half of the season, James suffered a hamstring injury causing him to struggle to maintain fitness. In a match against Nacional, he injured his hamstring once more and was subsequently substituted after the first half. The injury sidelined him for a month. On 1 February 2013, Porto bought back 30% economic rights of James from Gol Football Luxembourg for €8.57 million (by selling 47.5% economic rights of Diego Reyes for €3.5 million), which Porto sold in November 2010 for €2.5 million.

On 25 May 2013, it was announced that James had joined AS Monaco for a transfer fee of €45 million, the second most expensive transfer in Portuguese football behind former teammate Hulk. James subsequently signed a five-year contract that was set to keep him at the club until 2018. This transfer made him not only one of the most expensive transfers in the club’s history, but in Ligue 1 history as well, along as the one of the highest in world football.

James has been married to volleyball player Daniela Ospina, sister of David Ospina who is also a player on the Colombia national football team, since 2011 and has a daughter named Salome, born on 29 May 2013. On 27 July 2017, it was announced that the couple was in the process of divorcing.

On 22 July 2014, James confirmed the rumours by signing a six-year contract with the Spanish club for an undisclosed fee, which was reported to be approximately £63 million. At the time, this was the fourth-most expensive transfer in the world, the third-most expensive in Real Madrid’s history, and the most expensive Colombian to date after surpassing Radamel Falcao’s €60 million transfer in 2013. The amount spent on his transfer fee led many to referring James as a Galáctico credited by the fact that he was given the number 10 shirt carrying the legacy of Real Madrid legends such as Luís Figo, Ferenc Puskás and the player he admired the most while growing up and supporting the club, Zinedine Zidane.

James continued his play-making form by assisting the first goal and setting up the second against Belgium in a 2–0 victory. He was later voted man of the match. A few days later, James was praised once more as the man of the match in a 0–0 draw against the Netherlands. James started in Colombia’s 2014 opening match and scored a penalty against Tunisia in a 1–1 draw. In the last friendly before the World Cup, James scored yet another penalty against Jordan in a 3–0 victory.

On 2 June 2014, James was named in Colombia’s 23-man squad for the 2014 FIFA World Cup and assigned the number 10 shirt. In the team’s opening match of the tournament, James set up the first two goals, scored a last-minute goal with a low shot to seal a 3–0 victory over Greece and was named man of the match by FIFA. In the second match, James continued his form by scoring with a header and setting up a second goal for Juan Fernando Quintero in a 2–1 victory over Ivory Coast and was once again elected as man of the match. In the final group stage match against Japan, James came on as a second-half substitute and assisted two Jackson Martínez goals before scoring the final goal in a 4–1 victory. At the end of the group stage, James was ranked as the best performing player at the tournament by FIFA.

On 8 September 2015, during an international friendly match against Peru, James collided with Peruvian player Juan Manuel Vargas while going for a ball. Although he initially appeared able to continue, James was removed from the game as a precautionary measure, and he was diagnosed with a thigh muscle tear as a result of the knock. James was not seen back in training until 27 October 2015.

In 2015, Forbes estimated that James’ annual income was $29 million.

James made his first direct contribution towards qualification, scoring a goal in a heated duel against Copa America champions Chile, securing a 1–1 away draw. In early 2016, he provided both a goal and assist in a difficult away match against Bolivia resulting in a 2–3 victory. Days later, he assisted another goal in a 3–1 home victory against Ecuador. In early August, he contributed both a goal and an assist in Colombia’s 2–0 victory against Venezuela.

On 11 July 2017, it was announced that James was loaned to Bayern Munich on a two-year long deal. Bayern paid Real Madrid €13 million as a loan fee for the two season-long loan. With James’ loan deal to Bayern, he reunited with his old Real Madrid manager Carlo Ancelotti. Bayern had the option to buy James for €42 million at the end of the loan period. He scored his first goal of his loan spell in a 3–0 away win over Schalke 04. After a slow start to his Bayern career, mainly due to an injury in preseason, James rediscovered his form after Jupp Heynckes was hired as Bayern’s manager in October 2017 as the club sacked Ancelotti.

Starting off 2017, James scored a late dramatic goal against a defensive Bolivia after missing an earlier penalty. The 1–0 home victory allowed Colombia to move to 4th place within the qualification group. Days later, James would score and provide a goal in an impressive 0–2 victory in Ecuador. For his first friendly of the year, James assisted Radamel Falcao’s goal from the corner against European giants Spain. The game would end 2–2. Days later against Cameroon, James would both provide and score a goal in a dominating 4–0 victory. For the last qualification match of the 2018 World Cup, James would score a crucial away goal against South American rival Peru, resulting in a 1–1 draw and granting Colombia the last automatic qualification spot at fourth place. James’ last contribution of 2017 for Colombia would be an assist against South Korea, which would end 2–1.

On 2 April 2018, Bayern’s CEO, Karl-Heinz Rummenigge thanked Ancelotti for luring James to Bayern. “It was a very, very good transfer and I have to thank Carlo Ancelotti once again,” Rummenigge said.

On 15 September 2018, James scored his opening goal of the season in a 3–1 victory over Bayer Leverkusen. On 17 March 2019, he scored three goals in a 6–0 league win over Mainz, his first hat-trick since 2011, with Porto.

Colombia’s World Cup preparations in 2018 began against World Cup favorites France, where James provided two assists towards a comeback of a 2–0 score to a 2–3 victory. This marked the first victory in Colombia’s history over France.

On 4 June 2018, James was selected in Colombia’s 23-man squad for the 2018 FIFA World Cup in Russia. James did not start in the opening game against Japan after a calf injury during training. He came as a substitute in the 59th minute for Juan Quintero. On 24 June 2018, he provided two assists in a 3–0 victory over Poland and was named as the Man of the Match. James had to be substituted in the 30th minute in the final match of the group stage against Senegal due to the injury. James played in all three matches during the group phase, but was forced to sit out of Colombia’s last 16 match against England. Colombia lost 4–3 on penalties against England and were eliminated from the World Cup. James was unable to score in those three matches.

On 18 May 2019, James won his second Bundesliga title as Bayern finished two points above Dortmund with 78 points. A week later, James won his first DFB-Pokal as Bayern defeated RB Leipzig 3–0 in the 2019 DFB-Pokal Final. James did not appear in the match as he was out injured. James appeared in 28 matches and scored seven goals in all competitions.

On 5 June 2019, it was announced that Bayern Munich would not pick up the buy option and he would return to Real Madrid.

On 30 May 2019, James was included in the 23-man final Colombia squad for the 2019 Copa América. In the quarter-finals of the tournament against defending champions Chile on 28 June, following a 0–0 draw after regulation time, James scored in the resulting penalty shoot-out; however, Colombia were defeated 5–4 and were eliminated from the competition.

James joined Premier League club Everton in September 2020 on a two-year deal, with a club option for a third season. The deal once again reunited him with manager Carlo Ancelotti. He made his debut later that month in a 1–0 away win against Tottenham Hotspur in their first game of the 2020–21 Premier League season. The following week he scored his first goal for Everton in his home debut, a 5–2 league win against West Bromwich Albion. James scored two goals and provided an assist for his international teammate Yerry Mina in a 4–2 victory at Goodison Park against Brighton on 3 October 2020.