He played college football for the Texas Longhorns, where he won the 2006 Rose Bowl, and was selected by the Chiefs in the third round of the 2008 NFL draft.

Charles began his career as a backup to halfback Larry Johnson, rushing only 67 times for 357 yards in his rookie season.

[8] The Associated Press named him to their first-team all-state squad and he was declared the Houston Chronicle area offensive MVP.

[10] Charles is a two-time recipient of the Willie Ray Smith Award, which is given to the southeast Texas offensive MVP.

In the summer between his sophomore and junior years, Charles won the bronze medal in the 400m hurdles at the 2003 World Youth Championships in Athletics.

He led the 200 meter race after the preliminary round but elected not to participate in the final, as Texas had the Big 12 team title well in hand.

Charles's efforts helped the Longhorns earn a third place showing for the men's track and field team, the highest since a second-place finish at the 1997 NCAA finals.

Charles attended and played college football for the University of Texas from 2005 to 2007 under head coach Mack Brown.

[16][17][18] In his true freshman season with the Longhorns, Charles was an instant contributor in a crowded backfield that included Vince Young as a dual-threat quarterback.

[41] Despite his successes early in the season, Mack Brown and Greg Davis hinted that Charles could face less playing time as a result of his fumbling problems.

[43] Greg Davis said he wanted to get the ball to Charles "in space", on pitches and passes, instead of in heavy traffic up the center.

[44] On October 28, 2007, Charles rushed 33 times for 290 yards in the 28–25 victory, the most ever against the Nebraska Cornhuskers and the fourth-highest total in Texas Longhorns history.

[58] The Kansas City Chiefs selected Charles in the third round of the 2008 NFL draft with the 73rd overall pick, acquired from the Minnesota Vikings in the Jared Allen trade.

[64][65] In Week 9, with Larry Johnson out, Charles had 18 carries for 106 rushing yards in a 30–27 loss to the Tampa Bay Buccaneers.

[66] In Week 12, against the Buffalo Bills, Charles had his first professional touchdown on a 36-yard reception from quarterback Tyler Thigpen in the 54–31 loss.

[67] In Week 16, Charles had three catches for 102 receiving yards, including a 75-yard reception to help set up a Larry Johnson rushing touchdown, against the Miami Dolphins in the 38–31 loss.

[70] During Week 9 of the 2009 NFL season, Larry Johnson was released and Charles was promoted to first-string but split carries with Kolby Smith.

[73] In Week 11, in a 27–24 overtime victory over the Pittsburgh Steelers, Charles returned the opening kickoff 97 yards for a touchdown.

[76] In Week 14, against the Buffalo Bills, Charles ran for a 76-yard touchdown, one of the longest runs in Chiefs history, as part of a 20-carry, 143-rushing yard performance.

[112] He became the second player in franchise history, joining Larry Johnson, to record two games with at least 200 rushing yards in a single season.

[115] On the NFL Top 100 Players of 2013, he was ranked 20th by his peers[116] Charles started the 2013 season with scoring at least one touchdown in each of the first seven games.

In Weeks 12 and 14, he went over 150 scrimmage yards and scored two touchdowns in both games against the San Diego Chargers and Washington Redskins.

[118] Charles's performance made him the first Chiefs player to score five touchdowns in a game since Abner Haynes accomplished the feat for the Dallas Texans in 1961.

[121][122] Charles's performance was only the 11th game in NFL history where a player accounted for at least 30 points, the first since Clinton Portis accomplished the feat against the Chiefs in 2003.

[123] His 195 receiving yards were the fourth-most for a running back in a single game in NFL history and the most since Marshall Faulk had 204 against the Chicago Bears in 1999.

[126] In the Chiefs' Wild Card Round game against the Indianapolis Colts, Charles recorded three carries for 18 rushing yards before having to leave the 45–44 loss with a concussion in the first quarter.

[131] On July 23, 2014, one day after threatening to hold out of training camp, Charles agreed to a two-year, $18.1 million extension making him one of the top five highest paid running backs in the NFL.

[135][136] On October 19, against the San Diego Chargers, Charles passed Priest Holmes's mark of 6,070 rushing yards to become the all-time leading rusher for the Chiefs.

[146] In the loss, he had a key fumble late in the game that was returned for a touchdown by Bradley Roby and gave the Broncos the winning points.

[158] In the season opener against the Los Angeles Chargers, Charles had 10 rushes for 40 yards but lost a fumble in the 24–21 victory.