Sayers was inducted into the Pro Football Hall of Fame in 1977 at age 34 and remains the youngest person to have received the honor.

Sayers' younger brother, Ron, later played running back for the San Diego Chargers of the American Football League.

A fine all-around track athlete, he set a state long jump record of 24 ft 101⁄2 in (7.58m) as a senior in 1961.

[4] Sayers was recruited by several major Midwestern colleges before deciding to play football at the University of Kansas.

While being interviewed during a broadcast of a Chicago Cubs game on September 8, 2010, Sayers said he had originally intended to go to the University of Iowa.

Against Oklahoma State, he carried 21 times for a conference single-game-record 283 yards to lead Kansas to a 36–17 comeback victory.

In 1964, his senior year, he led the Jayhawks to a 15–14 upset victory over Oklahoma with a 93-yard return of the game's opening kickoff for a touchdown.

[17] He earned first-team All-America honors from each of the same selectors as in the previous year, in addition to the Associated Press (AP),[18] among others.

[20][21] He was the last NFL player to score a rushing, receiving, and kickoff return touchdown in the same game until Tyreek Hill accomplished the feat over 50 years later, in 2016.

"[23] On December 12, Sayers tied Ernie Nevers' and Dub Jones' record for touchdowns in a single game, scoring six in a 61–20 victory over the San Francisco 49ers that was played in muddy conditions at the Chicago Cubs' Wrigley Field.

The first of his kickoff return touchdowns that season came against the Los Angeles Rams, as he followed a wedge of blockers en route to a 93-yard score.

[34] Sayers was named to All-Pro first-teams by the AP, UPI, the NEA, The Sporting News, and the Pro Football Writers Association, among others.

Sharing more of the rushing duties with other backs, such as Brian Piccolo, Sayers gained 880 yards with a 4.7-yard average per carry.

[39] After the season, Sayers was chosen for his third straight Pro Bowl, in which he returned a kickoff 75 yards and scored a three-yard rushing touchdown and again earned player of the game honors.

[41] Sayers had the most productive rushing yardage game of his career on November 3, 1968, against the Green Bay Packers, during which he carried 24 times for 205 yards.

[44] Despite missing the Bears' final five games, he earned first-team All-Pro recognition from several media outlets, including the AP,[45] UPI,[46] and NEA.

He was kept out of the first three games after carrying the ball only twice in the preseason, as Bears head coach Jim Dooley planned to slowly work him back into the rotation.

[57] The following week, against the 49ers, he carried five times before injuring his ankle in the first quarter,[58] an injury that ultimately caused him to miss the remainder of the season.

Sayers' final game was in the 1972 preseason in which he fumbled twice in three carries; he retired from professional football days later at age 29.

[55][61] He possessed raw speed and was also highly elusive and had terrific vision, a combination which made him very difficult to tackle.

[62] Actor Billy Dee Williams, who portrayed Sayers in the 1971 film Brian's Song, likened his running to "ballet" and "poetry".

[68] In the Pro Bowl following his rookie season, he had kickoff returns of 51 and 48 yards, despite limited opportunities due to the East's attempts to punt and kick away from him.

[68] He was named the "Back of the Game", an honor he received again in 1968 and 1969, joining Johnny Unitas as the only players to win three Pro Bowl MVP awards.

He supported the Cradle Foundation—an adoption organization in Evanston, Illinois, and founded the Gale Sayers Center in the Austin neighborhood of Chicago.

The Gale Sayers Center is an after-school program for children ages 8–12 from Chicago's west side and focuses on leadership development, tutoring, and mentoring.

[38] In 2009, Sayers joined the University of Kansas Athletic Department staff as Director of Fundraising for Special Projects.

[77] In September 2013, Sayers reportedly sued the NFL, claiming the league negligently handled his repeated head injuries during his career.

[85] Sayers was elected to the Lincoln Journal's Nebraska Sports Hall of Fame in 1973, the first black athlete to be so honored.

[88] The Pro Football Hall of Fame selection committee named Sayers to its NFL 1960s All-Decade Team, which is composed of the best players of the 1960s at each position.

"[93] While he remained physically healthy, the disease had an adverse effect on his mental health and memory in particular, making simple tasks such as signing his own name difficult.