Carlos Salcido began his football career at his nearby home town team Chivas. He progressed through the ranks having successful seasons with the youth teams until he was called up to the senior team in 2001, making his official debut in the Primera División de México on 22 July 2001 in a 1–1 draw against La Piedad in 2001. Salcido disappeared from Chivas’ first squad until 2003, when he regained trust as a good defender. He would go on to play five half-seasons registering two goals in 105 matches. Salcido was a 2005 and 2006 Copa Libertadores Semifinalist with Guadalajara and a Runner-Up in Primera División (First Division), losing against UNAM Pumas in penalty shoot-outs in 2004. Salcido made his final league appearance for Guadalajara on 1 April 2006 against Pachuca in a 3-2 win.

In June and July following the 2006 FIFA World Cup, press speculation linked Salcido to several clubs in Europe, with one report claiming that he had agreed to sign for FA Premier League club Arsenal F.C. However, these speculations proved false as he signed a four-year contract with Dutch champions PSV Eindhoven on 10 July 2006.

Salcido was a first team regular in the Eredivisie under Coach Ronald Koeman, starting 33 of 34 league games in his first season at the club, which saw PSV crowned Dutch champions. On 18 November 2006, he scored his first goal in Europe, a spectacular long-distance goal in a match against Excelsior Rotterdam that ended 4–0. Salcido also appeared in the 2006-07 UEFA Champions League. In total Salcido played 48 Eredivisie and Champions League games that season, finishing 46 of them. For the 2007–08 season, Salcido was awarded the number 3 shirt, previously worn by Michael Reiziger. He was also named the team Vice-Captain after Timmy Simons was promoted to team Captain following the departure of former captain Phillip Cocu. In his second season at PSV Salcido played 33 games in the Dutch League, and 6 games in the Champions League, Salcido was crowned champion for the second straight year with PSV. In his third season with the club he played 28 games in the Dutch League scoring two goals. In 2009–10 Salcido played 27 Eredivisie matches and 9 UEFA Europa League matches. Salcido was a substitute for the beginning of the 2010–11 Eredivisie and the Europa League, where he did not appear in any matches but was soon transferred to Fulham of England.

Salcido debuted with Mexico 8 September 2004 in a 2006 world cup qualifying match against Trinidad and Tobago, he soon established himself with the number 3 shirt as the national sides first choice left back. He has gone on to appear in several international competitions with Mexico. In 2005, he played in the Confederations Cup in Germany, helping the Mexico national team to a fourth-place finish, where he appeared as a starter in all five matches. During a semi-final match against Argentina, Salcido scored a goal in extra time. He recovered the ball in the Mexican area, dribbled it past three defenders while going the entire length of the pitch, then scored after the shot fooled keeper Germán Lux when it bounced off Fabricio Coloccini.

Salcido was included in the 24-man squad selected on 2 April 2006, by head coach Ricardo Lavolpe, to play for the Mexico national team in the 2006 FIFA World Cup. Salcido played all four matches during the 2006 FIFA World Cup in Germany.

Salcido was called up by former Mexican national footballer now manager Hugo Sánchez for the 2007 Gold Cup. He announced that he would not participate in the 2007 Copa America with the team because he needed rest. He played in the final of the Gold Cup, where Mexico finished runner-up against rivals the United States. He was included in the tournament’s All-Tournament Team.

On 26 August 2010 it was announced that Fulham had agreed a £3.6 million deal with PSV to sign the player but the deal was still subject to the player agreeing terms. The deal was then finalised the next day. He made his debut against Blackburn Rovers on 18 September 2010. He contributed an assist in the 56th minute, when his cross pass fell to American player Clint Dempsey, who headed it into the net from 8 yards to level the game at 1–1. He played all 90 minutes. He left the club in August 2011 on loan to club Tigres UANL.

On 17 August 2011, it was announced that Salcido was transferred to Mexican side Tigres UANL on a season-long loan. After a robbery at his home in Claygate, London, Salcido requested to be transferred back to Mexico due to his family feeling unsettled. In his first season back in Mexico, Salcido helped Tigres win their third league title, and their first title in over thirty years.

On 7 March 2012, Fulham confirmed that Salcido had joined Tigres on a permanent basis.

On 20 May 2014, Guadalajara officially announced the signing of Salcido. After his participation at the World Cup, Salcido made his debut for Chivas de Guadalajara in a pre-season friendly match 9 July 2014 at the StubHub Center in Carson, California. Against Cruz Azul, the match ended in a 2–1 win for Guadalajara, with Salcido playing the entire match. Salcido made his first league appearance for Guadalajara 20 July 2014 in a match against Chiapas and played for the entire match. He scored his first goal from a penalty against bitter rivals America, on 24 November 2016.

Salcido announced his retirement from international football on 29 August 2014.

In January 2019, he officially joined Veracruz. On 4 February he made his debut against his former club Guadalajara in a 0–0 draw. He played his final match in the Liga MX on 23 November against his former club Guadalajara in a 1–3 loss.