Payton was one of three children born to Peter and Alyne Payton in Columbia, Mississippi. His father was a factory worker who had played semi-professional baseball. Payton was an active member of the Boy Scouts, Little League, and his local church. At John J. Jefferson High School, Payton played drums in the marching band, participated in the track team and sang in the school choir.

Payton's motto was "Never Die Easy", which is also the title of his posthumously published autobiography. Payton attributed this motto to Bob Hill, his coach at Jackson State. In practice, this meant that Payton refused to deliberately run out-of-bounds and always delivered some punishment to his tacklers before being forced off the field or forced down.  One of Payton's signature maneuvers was the "stutter-step", a high-stepping, irregularly paced run. He developed this as a way to distract his pursuers during long runs, saying that it startled them into thinking and gave him some advantage over players who were actually faster runners. In his autobiography, he likened the stutter step to a kind of "option play": when he was stutter-stepping, defenders would have to commit to a pursuit angle based upon whether they thought he would accelerate after the stutter-step, or cut -- he would read this angle and do the opposite of what the defender had committed to.  He re-invented the practice of stiff-arming his tacklers, which had gone out of favor among running backs in the 1970s. At times, he used his high school experience as a long jumper to leap over his opponents, landing on his head in the end zone to gain a touchdown in a game against the Buffalo Bills. His running gait was somewhat unusual, as his knees were minimally bent, and the motion was largely powered from the hip. This may have given his knees, a football player's most vulnerable joints, some protection, although he underwent arthroscopic surgery on both knees in 1983. He referred to this procedure as an 11,000-yard checkup.  After scoring touchdowns, Payton declined to celebrate; instead, he would often hand the ball to his teammates or the official. He disapproved of the growing practice of touchdown celebrations; he preferred post-game antics such as rushing into the locker room and locking his teammates out in the cold while taking a long shower. Although Payton would have won the respect of his peers and coaches by his running alone, he retired as the career leader in receptions for a running back with 492 for over 4,500 yards, and still holds the career record for a running back with 8 touchdown passes.

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