Williams was born on April 25, 1983 to his mother Sandra Hill. His mother was diagnosed with breast cancer in 2004. After ten years battling the illness, she died in May 2014. Four of his aunts have also had breast cancer. Williams now works with Susan G. Komen and has pink highlights in his dreadlocks to support the fight against breast cancer. In October 2019, he sponsored 500 mammograms to honor his mother.

Williams was considered the top running back in the state of Arkansas in 2001, having played for the Yellowjackets football team at Wynne High School in Wynne, Arkansas. He missed most of his sophomore season with a broken bone in his foot. 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. As a senior, he rushed for a single-season record 2,204 yards and 34 touchdowns, averaging 10.4 yards per carry while leading his squad to the state 4A championship. He had 939 yards rushing in four playoff games, including 26 carries for 302 yards and six touchdowns against Greenwood; in the state championship game against Stuttgart, he rushed for 194 yards on 24 attempts, scoring two rushing touchdowns, one receiving touchdown and one return touchdown. He was named the Arkansas Democrat-Gazette 2001 Offensive Player of the Year and was selected to the Associated Press Arkansas Super Team in 2001.

Williams was a letterman in track & field. He still holds the state 4A record in the 100-meter dash with an electronically-timed 10.81 seconds. He helped lead Wynne to a second-place finish in the 2001 state track championships.

In the 2003 regular season opener against Tennessee Tech, Williams had 61 rushing yards and one rushing touchdown in the 40–10 victory. He had career highs of 135 receiving yards and two receiving touchdowns playing against the Golden Eagles. The following week against Mississippi, he recorded 131 rushing yards, 36 receiving yards, and two rushing touchdowns in the 44–34 victory. He gained over 100 yards the following week against Southern Mississippi, finishing the game with 158 rushing yards, in the 23–6 loss. After a 108-yard game in a 38–16 victory over Arkansas State and another 107-yard game in a 24–10 loss to UAB the following week, he tied the school record with four consecutive games with at least 100 rushing yards. The game after, he broke the record, when he posted 119 rushing yards against Mississippi State in a 35–27 loss. He continued the streak against the Houston Cougars with 120 rushing yards and two touchdowns in a 45–14 victory. The next week he had a career-high, 195 rushing yards and two touchdowns, in the 41–9 victory against Tulane. Playing East Carolina, he made the record eight consecutive games with at least 100 rushing yards in the 41–24 victory. With the 137 yards rushing, he broke the school record for single season rushing yards. He continued to break records the next week, when he broke the school record for attempts in a single season. Williams had 154 rushing yard and one rushing touchdown on 27 attempts in the 37–7 victory over Louisville. 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. He ended the season with over 1,400 rushing yards, the most in school history, and leading the nation in all-purpose yards. He was named as the 2003 Conference USA Offensive Player of the Year.

After missing the last two regular season games and the New Orleans Bowl, Williams returned in the 2004 season opener against Mississippi. With 118 rushing yards in the 20–13 victory, he made it 11 consecutive games with over 100 rushing yards, continuing the streak he began the previous season, and having a career-high 37 attempts. While playing against Chattanooga, Williams gained 136 rushing yards, three rushing touchdowns, 87 receiving yards, and a touchdown reception in the 52–21 victory. His four touchdowns marked a career-high for a single game. His streak ended a few weeks later, at 13 when UAB held him to 92 rushing yards in the 35–28 loss. Williams’ junior season ended when he broke his leg while playing Bowling Green in the GMAC Bowl. He finished his junior year leading the nation with 22 rushing touchdowns and second with 1,948 rushing yards. For the second straight year, he was named as the Conference USA Offensive Player of the Year.

Williams started his senior season being held to 85 rushing yards in a 10–6 loss to Ole Miss but followed that up with ten consecutive games with over 100 yards rushing. While playing against Chattanooga, he rushed for 205 yards in the 59–14 victory. He recorded 223 yards in a 37–31 loss to Tulsa. The next week, he posted 236 rushing yards playing in a 27–20 victory over UTEP. After a few games, Williams accumulated 226 rushing yards and two touchdowns in a 27–24 victory over East Carolina. He finished the regular season with 127 rushing yards in a 26–3 victory over Marshall. In his final college game, the 2005 Motor City Bowl, Williams helped Memphis defeat the Akron Zips 38–31, by running for a Bowl record 238 yards and scoring three touchdowns. His performance made him the top ground-gainer in college football in 2005. Williams was also an All-America selection by the American Football Coaches Association (AFCA) and the Walter Camp Foundation.

Williams was a finalist for the 2005 Doak Walker Award, which was awarded to Reggie Bush. He came in seventh overall in the Heisman Trophy voting. In 2005, Williams was named the inaugural winner of the ARA Sportsmanship Award, presented by the Awards and Recognition Association to the Division I football player who best exhibits sportsmanship both on and off the field. For the third straight year, he was named as the Conference USA Offensive Player of the Year.

Though at one point he was considered a top ten pick, with some projecting him as high as #4 overall to the New York Jets, Williams saw his draft stock fall in weeks preceding the draft, as many teams filled their needs at the running back position via free agency. On April 29, 2006, he was selected by the Carolina Panthers in the first round with the 27th overall pick in the NFL Draft. He joined Reggie Bush, LenDale White, Laurence Maroney, and Joseph Addai, among others, in a promising draft class at running back. He became the highest drafted player out of the Memphis Tigers program since Bob Rush went 24th overall in 1977. In addition, he became the highest drafted running back from the Memphis Tigers. Williams adopted the jersey #34, which he wore in high school, and which was the same as his hero at the time, Ricky Williams.

In the 2007 season, Williams continued to back up DeShaun Foster. He had his first 100-yard game of the season in Week 6 against the Arizona Cardinals with 10 carries for 121 rushing yards. 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. On the next play, he ran the ball to the right corner of endzone for his first touchdown of the season. The next five weeks, he had 97 total rushing yards due to limited playing time. 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. He finished the season with 144 carries for 717 rushing yards and led the team with four rushing touchdowns. He finished ninth in the NFL in yards per carry (5.0).

During the 2010 Pro Bowl, Williams scored a touchdown on a seven-yard run, the first by a Panthers player in team history. He finished the game with two carries for six yards and a touchdown, as well as a 15-yard reception.

On October 24, 2010, Williams injured his right foot during the Panthers’ home win against the San Francisco 49ers in Week 7. He did not play again before being placed on injured reserve on November 17, 2010, with what was announced to be a mid-foot sprain. Williams finished the year with 361 rushing yards and one rushing touchdown on 87 rushes to go along with 11 receptions for 61 receiving yards. On July 27, 2011, Williams signed a five-year, $43 million contract extension to stay with the Panthers.

In 2011, the Panthers drafted Cam Newton as their starting quarterback. This resulted in a three-way split for carries between Williams, Stewart, and Newton. Williams helped the trio finish third in the league in total rushing yards with 2,408. The Panthers finished first in average yards per carry and first in total touchdowns with 26. Williams finished the season with 155 carries for 836 rushing yards and seven rushing touchdowns to go along with 16 receptions for 135 receiving yards.

In 2012, the Panthers signed former San Diego Chargers fullback Mike Tolbert. The signing meant that Williams’s carries would be split further with Stewart, Newton, and Tolbert. In Week 17, against the New Orleans Saints, he rushed 21 times for a career-high 210 rushing yards and two rushing touchdowns in the 44-38 victory. Although he played every game of the season, he only started 10 of the games. He recorded 737 yards on 173 attempts. He scored five rushing touchdowns and two receiving touchdowns.

In Week 3 against the New York Giants, Williams had 23 carries for 120 rushing yards in the 38-0 victory. In Week 15 against the New York Jets, he had 168 scrimmage yards and a receiving touchdown in the 30-20 victory. In the 2013 season, Williams had 201 carries, his most attempts since his Pro Bowl season in 2009. However, he did not make much out of these carries, only rushing for 843 yards. He scored three rushing touchdowns, his fewest since his injury plagued season in 2010, and one receiving touchdown.

Williams rushed for 72 yards on 12 attempts in the season-opening 20–14 victory over the Tampa Bay Buccaneers. He missed the second and third games of the season against the Detroit Lions and the Pittsburgh Steelers respectively, because of a hamstring injury that he suffered during a practice in between week one and two. In a Week 4 loss versus the Baltimore Ravens, Williams suffered a high ankle sprain and was taken out of the game. His cast was removed on October 6, 2014. Coach Ron Rivera has said that Williams would be able to return for week nine. In a Week 13 loss to the Minnesota Vikings, Williams fractured his right middle finger. He was listed as day to day. He missed a Week 14 victory over the New Orleans Saints due to his hand injury. He was listed as doubtful for the week fifteen game versus the Tampa Bay Buccaneers. After missing the final two games of the season versus the Cleveland Browns and the Atlanta Falcons respectively, Williams returned for the Wild Card Round versus the Arizona Cardinals. He saw very limited action, only carrying the ball four times for 16 yards and no receptions in a 27–16 victory. In the Divisional Round game versus the Seattle Seahawks, Williams carried the ball two times for 14 yards in a 31–17 loss. He was released on March 10, 2015.

On March 13, 2015, Williams signed a two-year contract with the Pittsburgh Steelers. The contract was for two years and $4.0 million, with $1.13 million guaranteed, and a signing bonus of $1.13 million.

In his first start since Week 2, Williams had a season-high 27 carries for 170 yards and scored two touchdowns, while accounting for 55 receiving yards on two receptions in a Week 9 victory over the Oakland Raiders. On December 13, 2015, he had 23 rushes for 76 yards and two rushing touchdowns in a win over the Cincinnati Bengals.

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. After two weeks in the 2016 season, he was the league leader in rushing yards after rushing for 146 yards against the Washington Redskins in the season opener and 94 yards on a career-high 32 carries against the Cincinnati Bengals in the next game. For his Week 1 performance, he earned AFC Offensive Player of the Week. His production dipped later on the season and he finished with 343 rushing yards and four rushing touchdowns. The Steelers made the playoffs and advanced to the AFC Championship. In the 36–17 loss to the New England Patriots, he had 14 carries for 34 rushing yards and a rushing touchdown to go along with seven receptions for 51 yards. In addition, he had a successful two-point conversion in what was his final professional game. On June 25, 2018, he announced on Facebook that he had retired from the NFL.

Accompanied by Barnidge and Austin Dillon, Williams made his debut at Slammiversary XV on July 2, 2017, teaming with Moose (himself a former NFL player) in a victory over Chris Adonis and Eli Drake. 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 wrestlers such as Matt Riddle, Akiyama, and Kurt Angle. Bryan Alvarez stated that Williams was “pretty damn amazing in his first-ever match”. Meltzer later stated that Williams had the best in-ring performance by a celebrity in wrestling history.

Williams announced his retirement from wrestling on July 5, 2017.

On July 2, 2018, Williams announced he is returning to wrestling and will wrestle again for Impact. Williams began a storyline with Austin Aries, but has not appeared since after one episode