Dudley was drafted in the 1942 NFL Draft with the first overall pick by the Pittsburgh Steelers. During the 1942 season, he led the league in rushing with 696 yards on 162 carries and was then named to the All-Pro team. He also completed 35 of 94 passes for 438 yards and two touchdowns, punted 18 times for a 32.0 average, returned 20 punts for 271 yards (14.0 avg), and ran back 11 kickoffs for 298 yards (27.0 avg), scoring once. In the first game of his professional career, Dudley ran for a 55-yard touchdown and in his second game scored on a kickoff return.
In 1942, the U. S. armed services began drafting all eligible young men to fight in World War II. Dudley originally enlisted and was sworn into the Naval Air Corps, however they found out he needed to have his parents' consent, since he wasn't twenty-one. Dudley then enlisted in U. S. Army Air Corps in September 1942, but there was an influx of recruits and Dudley was told he would have to wait three months before he began training. This delay made it possible for him to finish his rookie season with the Steelers.
Dudley returned to Pittsburgh that fall and rejoined the Steelers's team for the last four games of the 1945 season. In a game against the Chicago Cardinals, he ran for two touchdowns and kicked for two additional points and became the Steelers' leading scorer for that season. He also rushed for 204 yards and returned three kickoffs for 65 yards.
In 1946, the Steelers hired a new coach Jock Sutherland and Dudley scored 48 points, which contributed to the Steelers' 5-5-1 record. During that season, he became the league leader in rushing (604 yards), interceptions (10 total which he returned for 242 yards) and punt returns (27 total for 385 yards). In doing this, Dudley became the only NFL player to lead in four unique statistical categories. He was named All-Pro and was awarded the NFL's Most Valuable Player Award. Dudley became the first (and as of 2007, only) person to win MVP awards in college, service, and professional levels.
"Despite his lack of breakaway speed, Bill was the most feared kickoff returner in the game. He passed sidearm, like a kid, yet he had a fine completion average. He was 'too small,' but he was hardly ever hurt too badly to play. He was the league's top ground gainer, yet he was also one of the fiercest defensive tacklers and the best in the game at interceptions. As one of the men who faced him ruefully admitted, Bill could not throw a pass correctly and 'ran as if he was staggering,' yet he could always find a way to beat you."
Dudley was traded to the Detroit Lions after 1946, where he was offered three-year contract and $20,000 a season. He was elected captain of his team all three years, 1947–1949. During his first year with the Lions, the team finished last. On October 19, 1947 against the Chicago Bears, Dudley returned a punt for an 84-yard touchdown. During 1947, he scored 13 touchdowns; seven on pass receptions, four on runs from scrimmage, one on a punt return, one on kickoff return and throwing two. In his last season with the Lions, he led Detroit in scoring for the third year in a row.
At the end of the 1949 season, Lions coach Bo McMillin traded Dudley to the Washington Redskins, where he played for three seasons, during which he led the team in scoring every year. On December 3, 1950 Dudley fielded a 60 yard punt kicked by Steelers' player Joe Geri. He ran over 30 yards before he reached his hands out of bounds, while keeping both feet in bounds, and caught the punt at the Redskin’s four yard line, and then ran it for a 96-yard touchdown. Dudley took a break during the 1952 season but returned in 1953. He retired at the end of the season due to knee injuries and an overall physical deterioration.
Dudley was named first- or second-team All-NFL six times in his career and was named to three Pro Bowls. During his nine pro seasons, Dudley gained 3,057 yards on 765 rushing attempts, a 4.0 average, and scored 20 touchdowns; caught 123 passes for 1,383 yards and 18 touchdowns; returned 124 punts for 1,515 yards and three touchdowns; ran back 78 kickoffs for 1,743 yards and one touchdown; intercepted 23 passes and returned them for 459 yards and two touchdowns; and punted 191 times for a 38.2-yard average. He added 121 extra points and 33 field goals to his 44 touchdowns for a total of 484 points. Dudley led his team in scoring during every one of his nine NFL seasons.
Dudley is the only player ever with a rushing touchdown, touchdown reception, punt return for touchdown, kickoff return for touchdown, interception return for touchdown, fumble return for a touchdown, and a touchdown pass. He also had a touchdown via lateral and kicked PATs and field goals.