Adrián González was born in San Diego, California to David and Alba González, both Mexican natives. González is the youngest of three boys; his brothers are David Jr. and Edgar, a former big leaguer. After his birth, his parents moved the family to Tijuana, where his father owned an air-conditioner business. The three boys grew up playing baseball in Mexico, where their father had been a member of the Mexican national baseball team. In 1990 the family returned to the United States, settling in Bonita, California.

In June 2000, González became the first infield position player to be drafted first overall since Alex Rodriguez in 1993. He was given a $3 million signing bonus by the Florida Marlins. While in the Marlins organization, González played with the Gulf Coast League Marlins, Kane County Cougars, Utica Blue Sox, Portland Sea Dogs (2002), Albuquerque Isotopes (2003), and Carolina Mudcats (2003). With the A level Kane County Cougars in his 2nd professional season, González hit .312 with 17 home runs and 103 RBIs in 127 games. As a result, he was selected by the Midwest League as the Most Valuable Player & Top Prospect in the league. He also played in the All-Star Futures Game.

After a wrist injury, the Marlins felt González would be hindered swinging the bat, so the Marlins included González in a June 2003 trade with the Texas Rangers, along with Ryan Snare and minor leaguer Will Smith, to acquire a relief pitcher, Ugueth Urbina, to aid their championship drive. González played with the Rangers’ Class AA team, the Frisco RoughRiders until he made his Major League debut against the Seattle Mariners on April 18, 2004. He was hitless in 3 at-bats. He recorded his first base hit on April 20 against Ramón Ortiz of the Anaheim Angels and his first home run on April 25 off Kevin Jarvis of the Seattle Mariners. He played in 16 games for Texas in 2004 and in 43 games in 2005, with a combined batting average of .229 and 7 homers.

With extended playing time at first base in 2006, González continued to improve his hitting and defense. On July 23, 2006, he was named the NL Player of the Week. In his first full season, he led the Padres in batting average (.304) and home runs (24). He was the first player in Petco Park history to have more than one multiple home run game. He was named the Padres’ MVP for 2006.

González opened the 2015 season with five home runs in the first three games of the season, including three on April 8 against Andrew Cashner. He was the first MLB player to hit five home runs in the first three games of the season. By homering in his fifth consecutive game, dating back to the end of the 2014 season, he tied the team record, which he shares with Roy Campanella (1950), Shawn Green (2001), Matt Kemp (2010), and Joc Pederson (2015). He won the player of the week honors as a result of that performance. He was also awarded with the National League player of the month award for April as he hit .383 with eight home runs and 19 RBI in the month. He recorded his 1,000th career RBI when he hit a two run home run off Julio Teherán of the Atlanta Braves on May 26. Gonzalez was selected to the 2015 Major League Baseball All-Star Game, the first Dodger first baseman selected since Nomar Garciaparra in 2006. He finished the 2015 season by hitting .275 in 156 games with 28 home runs and 90 RBI, the lowest RBI total he had since 2006.

On March 31, 2007, González agreed to a $9.5 million, four-year deal, with a club option for $5.5 million in 2011. In the 2007 season, he led the Padres in home runs again, with 30, and had a team-high 100 RBIs. He led all Major League first basemen with 161 games and a career-high 46 doubles.

While Adrián was drafted by the Florida Marlins out of high school, his brother Edgar Gonzalez attended San Diego State University and was selected by the Tampa Bay Rays in the 30th round of the 2000 draft. Edgar debuted in the major leagues as a utility man with the San Diego Padres in 2008, joining his brother as a teammate.

In the 2008 season, González finished with a .279 average and once again led the Padres with 36 HRs and 119 RBIs. He was elected to the 2008 MLB All-Star Game as a reserve. He went 1 for 3 with a single and a sacrifice fly, scoring Miguel Tejada of the Houston Astros. He won his first Gold Glove Award in 2008 at first base. González set career highs in games played (162), home runs (36), RBI (119), runs scored (103), walks (74) and slugging percentage (.510). He was named the Padres MVP for the second time.

González played winter ball in the Mexican Pacific League with the Venados de Mazatlán. In the 2009 Caribbean Series, he led his team past the Dominican Republic’s Tigres del Licey with a record-setting 3 home runs on February 4.

He led the majors in walks in 2009 with 119 and set a Major League record with eight consecutive multi-walk games, a record which still stands as of 2020. He also hit 40 home runs for the first time in his career. He was named the Padres team MVP for 2009, his third time honored.

During the 2010 season, González had 176 hits in 591 at-bats, good for a .298 batting average, his highest since hitting .304 in his first season with San Diego (2006). He had 93 walks and 114 strikeouts. His 93 walks put him in third place in the NL behind only Prince Fielder (114) and Albert Pujols (103). He finished with 31 home runs and 101 RBI, the third time in his career he had 100 RBI or more. González played in 160 games on the year, tying him with Rickie Weeks for 5th in the NL. He scored 87 runs on the season, compiling 302 total bases, which also tied him with Weeks, for 6th in the NL. González was named team MVP for the third consecutive year and the fourth time overall with the Padres.

On December 6, 2010, González was traded to the Boston Red Sox for a package of right-handed pitcher Casey Kelly, first baseman Anthony Rizzo, outfielder Reymond Fuentes, and a player to be named later, later determined to be Eric Patterson.

On April 15, 2011, González and the Red Sox agreed to a seven-year contract extension worth $154 million through the 2018 season.

On June 19, 2011, González hit his 1,000th career hit: a triple off of Milwaukee Brewers pitcher Yovani Gallardo.

On July 3, 2011, González was selected to represent the Red Sox at the 2011 All Star game in Arizona along with teammates Josh Beckett, Jacoby Ellsbury, David Ortiz, Kevin Youkilis, and Jon Lester. González hit a home run in the game and was responsible for the only run for the American League. Additionally, Ortiz selected González as one of three sluggers to join him in the Home Run Derby, where he finished second to Robinson Canó. González tied a record for most home runs in the final round of the home run derby at 11, which was then surpassed by the victor Cano.

González was named AL Player of the Month for June 2011 with a .404 average (40 for 99) – the best in the Majors for that month. After placing second in the 2011 Home Run Derby, González faced a home-run slump until he hit five home runs in ten at-bats on August 23–25.

In 2012 David and Alba González were named 2012 George and Barbara Bush Little League Parents of the Year. In November 2012, González was honored as one of 30 “exemplary citizens” by the Mayor of Tijuana in an official ceremony.

In 2012, González appeared in 123 games with the Red Sox, hitting .300 with 15 homers and 86 RBI.

On August 25, 2012, González was traded to the Los Angeles Dodgers (along with Josh Beckett, Nick Punto and Carl Crawford) and $11 million in cash for James Loney, Iván DeJesús Jr., Allen Webster and two players to be named later (Jerry Sands and Rubby De La Rosa). In his first at bat with the Dodgers that same day, he hit a three-run home run against the Miami Marlins. In 36 games with the Dodgers, he hit .297 with 3 homers and 22 RBI.

In the 2013 season, González appeared in 157 games for the Dodgers and hit .293 with 22 home runs and 100 RBI. He was a candidate for the final vote at the 2013 Major League Baseball All-Star Game but did not get selected to the game.

In the 2013 NLCS Game 5 against the St. Louis Cardinals, González went 3 for 4 with 2 home runs. The Dodgers would eventually lose the series in six games.

González played for the Mexico national baseball team in the World Baseball Classic qualifiers during spring training in March 2016. The team was managed by his brother Edgar. On June 22, 2016 during a game against the Washington Nationals, Gonzalez made a highlight-reel catch after a ball in foul territory deflected off Chase Utley’s glove and off Gonzalez’s leg. On August 7, 2016 González hit his 300th career home run against the Boston Red Sox. On the season he appeared in 156 games, with a .285 batting average, 18 homers and 90 RBI. It was the fewest home runs he had hit in a season since 2012.

On May 5, 2017, González was placed on the 10-day disabled list due to right elbow soreness. It was the first time in his MLB career that González was put on the DL. González recorded his 2,000th career hit with a double off Johnny Barbato of the Pittsburgh Pirates on August 22. González dealt with lingering back issues during the 2017 season, which caused him to spend half the season on the disabled list and as a result lost playing time to rookie Cody Bellinger at first. For the 2017 season, González only appeared in 71 games, batting .242/.287/.355 with 30 RBIs. He was shut down for the season in September and did not appear on the Dodgers playoff roster. In his final at-bat with the Dodgers, Gonzalez hit a home run against the Padres, giving him the rare distinction of having homered in both his first and last at-bats with the team.

On December 16, 2017, the Dodgers traded González, Charlie Culberson, Scott Kazmir, Brandon McCarthy, and cash considerations to the Atlanta Braves for Matt Kemp. Immediately following the trade, the Braves designated González for assignment and then released him two days later. González had to waive his no-trade clause to facilitate the trade, and he said that he did so because he wanted to test the free agent waters and see what other opportunities were out there for him.

On January 18, 2018, González signed a one-year contract with the New York Mets.

On June 10, 2018, the Mets granted González his unconditional release. In 54 games with the Mets, he batted .237/.299/.373; he had just three hits in his final 27 at bats with the team.