As a junior, he gained 1,044 yards rushing and scored 14 touchdowns, leading him to be named to the Arkansas All-State team in 2000.

While playing Louisville, he suffered a knee sprain and was forced to sit out the next week's contest against Mississippi State.

[20] The next week, in a win against Cincinnati, he posted 136 rushing yards but tore his MCL during the 21–16 victory, ending his record-breaking season.

In three separate games, Williams scored 24 total points, which remains a school record to this day albeit tied with four other players.

[43] He continued his productive season the next week when he accumulated 226 rushing yards on 39 carries and two touchdowns in a 27–24 victory over East Carolina.

Williams was also an All-America selection by the American Football Coaches Association (AFCA) and the Walter Camp Foundation.

[28] He holds the Division I National Collegiate Athletic Association (NCAA) record for 100-yard rushing games (34) and All-purpose yards (7,573).

[55] On March 24, at the Pro Day on the University of Memphis campus, Williams ostensibly improved his draft stock even further with an exceptional workout.

He joined Reggie Bush, LenDale White, Laurence Maroney, and Joseph Addai, among others, in a promising draft class at running back.

[60] Williams played in the first five games of the 2006 season and looked promising as an alternative to DeShaun Foster in the Carolina backfield, compiling an average of 5.3 yards per carry.

[64] In Week 11 against the St. Louis Rams, Williams filled in for Foster, who had injured his elbow, and totaled 20 carries for 114 rushing yards in the 15–0 victory.

In the fourth quarter, he clinched the 25–10 victory with a 75-yard run, the longest in team history, only to be tackled short of the goal line.

[71] In the final week of the regular season, Williams rushed for 121 yards on 20 carries while scoring two touchdowns in the 31–23 victory over the Tampa Bay Buccaneers.

[81] In Week 14, Williams was selected FedEx Ground Player-of-the-Week after a dominating performance in which he rushed for 186 yards on 19 carries and two touchdowns against the Tampa Bay Buccaneers.

[94] In Week 7, Williams recorded a 77-yard run against the Arizona Cardinals for the longest rushing play in franchise history, breaking his own mark set in 2007.

[101][102] During the 2010 Pro Bowl, Williams scored a touchdown on a seven-yard run, the first by a Panthers player in team history.

[122] In a Week 4 loss versus the Baltimore Ravens, Williams suffered a high ankle sprain and was taken out of the game.

Williams made his first career start as a Steeler on September 10 in the NFL season opener against the New England Patriots.

[141] Despite his success in the first two weeks of the season, Williams was used as a backup once All-Pro starter Le'Veon Bell returned from his two-game suspension.

In Bell's first game back, Williams received only one carry for two yards in a Week 3 12–6 victory over the St. Louis Rams.

[143] On October 28, Williams was fined $5,787 for wearing eye black that read "Find the Cure" in honor of breast cancer awareness.

[144] During a Week 8 loss to the Cincinnati Bengals, Williams rushed for 71 yards on nine carries and came in the game for Le'Veon Bell, who left with an injury.

[145] It was reported that Bell had sustained a torn MCL and would miss the rest of the season, effectively making Williams the starting running back.

[152][153] At the age of 32, he became the oldest player to at least hold a share of the NFL rushing touchdown single-season mark since Marcus Allen in 1993.

[154] Williams was again called upon to serve as the Steelers lead running back after another Le'Veon Bell suspension, this time for the first three games of the season.

[163] Williams appeared on the April 2, 2017, episode of Impact Wrestling, alongside former NFL tight end Gary Barnidge, to save Moose from an attack.

[166] Accompanied by Barnidge and Austin Dillon, Williams made his debut at Slammiversary XV on July 2, 2017, as a face, teaming with Moose (himself a former NFL player) in a victory over Chris Adonis and Eli Drake.

[167][168][169] His performance in the match received rave reviews from critics, including journalist Dave Meltzer, who stated that Williams "has the potential to be one of the greatest wrestlers I've ever seen", and compared him to other athletes turned professional wrestlers such as Matt Riddle, Jun Akiyama, and Kurt Angle.

[177] Williams now works with Susan G. Komen and has pink highlights in his dreadlocks to support the fight against breast cancer.

[180] Williams competed on the 32nd season of The Amazing Race with fellow former football player Gary Barnidge and finished in fourth place.