Parker played in (and started) all 16 regular season games. He compiled 1,494 yards on 337 carries (4.4 average) with 13 rushing touchdowns. He also had 12 runs of 20+ yards. Parker also caught 31 passes for 222 yards (7.2 average) and 3 touchdowns. In addition, his 16 combined scores broke the previous Steelers single-season touchdown mark of 15 set by Louis Lipps in 1987. Parker served as a backup to LaDainian Tomlinson and Larry Johnson in his first Pro Bowl, where he would finish the game with 40 yards on 2 carries.

In his second year, Parker earned the starting job after both Bettis (hamstring) and Staley (knees) missed the first part of the season with injuries. By default, Parker had to play the first game against the Tennessee Titans. He impressed Bill Cowher, as well as Titans coach Jeff Fisher, by gaining 161 rushing yards on 22 attempts (7.3 average). After following this performance with another 100+ yard game against the Houston Texans, Cowher gave Parker the starting position. “Fast Willie” started 15 of 16 games that season (being injured week 9 against the Green Bay Packers and missed the week 10 contest against the Cleveland Browns), finishing with 255 carries for 1,202 yards (4.7 average, a career long 80 yard touchdown run in week 16 against the Browns) and 4 touchdowns. He also finished the season with 218 yards receiving and one touchdown. Parker was the first Steeler back since Bettis in 2001 to top 1,000 yards in a season. Also, he is the second undrafted running back to rush for over 1,200 in the history of the NFL.(Along with Priest Holmes)

Parker was an undrafted free agent with the Steelers in 2004. While at UNC, Parker displayed great speed, but little vision, resulting in inconsistent play which led to him being benched in favor of Ronnie McGill during his senior year. However, some believe this is an indictment of the UNC Coaching Staff at the time, rather than Parker himself.

In 2006, Parker signed a major contract with the Steelers, a four-year $13.6 million deal that would solidify his future role on the team. Bill Cowher was quoted as saying that Parker would be a workhorse and receive the goal-line carries in his role as the starter, guaranteeing him the starring running-back role in Pittsburgh.

On November 12, 2006, in a home game against the New Orleans Saints, Parker rushed for 213 yards on 22 carries and two touchdowns, coming 5 yards short of the highest single-game rushing total in Steelers history. His two long gains of 72 and 76 yards set up touchdowns that capped off the Pittsburgh victory, 38–31. His 76-yard sprint late in the 4th quarter was the longest rush in Heinz Field history.

Parker was productive in 2007 as well, rushing for 1,316 yards but only 2 total touchdowns. He had eight 100-yard plus games, leading the league in that category and earning a second consecutive Pro Bowl berth before being injured late in the season. Parker suffered a broken right fibula early in a game against the St. Louis Rams on December 20, 2007, ending his season. He was replaced by backup Najeh Davenport. Parker led the league in rushing yardage at the time of his injury.

Coming off of his broken leg near the end of the 2007 campaign, there were questions surrounding Willie Parker’s ability to recover. He played little in the preseason, giving way to Rashard Mendenhall for much of the time. The first game of the year was against the Houston Texans. In this game, Parker would record 138 rushing yards and a career-high 3 touchdowns, all before the fourth quarter ever started. The Steelers got up 35–3 in the third quarter, and opted to pull some of their starting players. He was the leading AFC rusher for the week and was named the AFC Offensive Player of the Week. However, Parker suffered a knee injury four games into the season, leading to five missed games. His back-up, Rashard Mendenhall, suffered a shoulder injury and was placed on injured reserve. The third-string running back, Mewelde Moore, produced well in Parker’s absence, with 908 yards from scrimmage. Parker had four 100-yard performances, while compiling 791 yards on 210 carries, for a 3.8 average (worst of his career), and five touchdowns. He added only three receptions for 13 yards for an average of 4.3 yards per catch. Against the Chargers, Parker had his first 100+ yard game of his playoff career, compiling 146 yards on 27 carries and two touchdowns. The Steelers reached the Super Bowl again in 2008 and played Arizona Cardinals at Super Bowl XLIII. In Super Bowl XLIII, Parker was not able to make a significant impact, as the Pittsburgh Steelers were unable to establish a strong rushing game. He had 19 carries for only 53 yards, bringing his average to a mere 2.8 yards per carry, and no touchdowns. Regardless, with Ben Roethlisberger at the helm establishing the passing game, the Steelers went on to collect their sixth championship ring in Super Bowl XLIII, becoming the first team in NFL history to obtain that amount.

On April 2, 2010, Parker signed with the Washington Redskins, adding a third running back to Washington’s committee of Clinton Portis and Larry Johnson. He was released during final cuts on September 4, 2010.

On April 26, 2011, NFL.com reported that the Virginia Destroyers claimed Parker, along with many other free agent NFL players. The Virginia Destroyers are semi-professional team that was a member of the United Football League now a member of the National Gridiron League. Although Parker had made comments about wanting to go back to the Steelers, he ended up signing with the Destroyers.

Parker became an assistant coach for the West Virginia Wesleyan College football team in July 2012.

Beginning in 2015, Parker became running backs coach at Heritage High School in Wake Forest, North Carolina. Former NFL player Dewayne Washington is the head coach and Torry Holt serves as assistant head coach and wide receivers coach.