Payton played football in high school and at Jackson State University in Mississippi. It was during his college years that he gained the sobriquet “Sweetness” for his affable personality and graceful athleticism. In 1975 he was drafted by the NFL Chicago Bears. Payton played his entire career (12 seasons) with the Bears, filling the position of halfback for most of that time. He set NFL records for total career rushing yardage (16,726 yards), most combined career yards gained (rushing and pass receiving, 21,803 yards), most seasons with 1,000 or more yards rushing (10), most yards gained in a single game (275 yards), most games with 100 or more yards gained in a career (77), and most career touchdowns earned by rushing (110).

Besides being an outstanding rusher, Payton was a capable blocker, pass receiver, and even passer. He was best known, however, for his pinball running style, in which he often bounced off would-be tacklers. His rigorous off-season training regimen contributed to his durability; he started in more than 180 consecutive games in his career.

Payton was inducted into the Pro Football Hall of Fame in 1993. Established in 1987, the Walter Payton Award is presented annually to the top player in Division I-AA college football. During his final year of life, while suffering from a rare liver disease, Payton was credited with awakening national interest in organ donation.