Sayers, who had been diagnosed with dementia several years ago, was 77.
Known as the "Kansas Comet" for his college career at the University of Kansas, Sayers spent his entire seven-season career with the Bears and was inducted into the Pro Football Hall of Fame in 1977, but he was also known by many for the movie that told the story of his friendship with a dying teammate, Brian Piccolo.
Sayers, in a well-known line, said: “I love Brian Piccolo, and I’d like all of you to love him, too."
"My heart is broken over the loss of my dear friend, Gale Sayers," the actor Billy Dee Williams, who starred in the movie, said in statement.
"Portraying Gale in 'Brian’s Song' was a true honor and one of the (highlights) of my career. He was an extraordinary human being with the kindest heart."
NFL Commissioner Roger Goodell praised Sayers for his play on the field and his compassion off it.
"The NFL family lost a true friend today with the passing of Gale Sayers," Goodell said in a statement. "We will also forever remember Gale for his inspiration and kindness. Gale's quiet unassuming demeanor belied his determination, competitiveness and compassion."
Sayers averaged 5 yards per carry, ranking him among the game’s all-time greats, like Jim Brown and Barry Sanders. Injuries shortened his career to just 68 games over seven seasons, from 1965 to 1971.
"He was the very essence of a team player — quiet, unassuming and always ready to compliment a teammate for a key block," Hall of Fame President and CEO David Baker said of Sayers. "Gale was an extraordinary man who overcame a great deal of adversity during his NFL career and life."
Sayers was one of the most elusive runners of his time and once scored six touchdowns in one game — four rushing, one catch and one punt return — during a 1965 clash against the San Francisco 49ers.
“Football fans know well Gale’s many accomplishments on the field: a rare combination of speed and power as the game’s most electrifying runner, a dangerous kick returner, his comeback from a serious knee injury to lead the league in rushing, and becoming the youngest player inducted into the Pro Football Hall of Fame,” Bears chairman George McCaskey said in a statement.
“People who weren’t even football fans came to know Gale through the TV movie ‘Brian’s Song,’ about his friendship with teammate Brian Piccolo. Fifty years later, the movie’s message that brotherhood and love needn’t be defined by skin color still resonates."
Sayers’ place in NFL and pop culture lore was cemented by his friendship with Piccolo, in a relationship brought to life by actors Williams and James Caan in the 1971 movie.
Sayers, who was Black, and the white Piccolo became friends and roommates when the team was on the road. The interracial pairing was considered groundbreaking in the late 1960s.
Piccolo was stricken with an aggressive form of testicular cancer that would eventually take his life on June 16, 1970. He was 26 years old.
Just three weeks before Piccolo’s death, Sayers spoke at the Pro Football Writers Awards Dinner in New York City, accepting the 1969 George S. Halas Most Courageous Player Award for overcoming a serious knee injury to lead the league in rushing.
Sayers used that platform to pay tribute to his dying friend.
“Compare his courage with the kind I’m supposed to possess,” Sayers said that night. “There was never any doubt that I’d return, knee injury or no. But think of Brian and his fortitude in the months since last November, in and out of hospitals, hoping to play football again, but not too sure at any time what the score was or might be. He has the heart of a giant. He has the mental attitude that makes me proud to have a friend who spells out the word ‘courage’ 24 hours a day, every day of his life.”
“You flatter me by giving me this award, but I tell you here and now that I accept it for Brian Piccolo," Sayers continued. "Brian Piccolo is the man of courage who should receive the George S. Halas Award. It is mine tonight, it is Brian Piccolo’s tomorrow."
Playing in an era long before the internet and years ahead of 24-hour cable news, most Americans only know this famous line — “I love Brian Piccolo” — through Williams and “Brian’s Song.”
“I love Brian Piccolo, and I’d like all of you to love him, too," Sayers said. "And tonight, when you hit your knees, please ask God to love him.”
Caan, who made "Brian's Song" a year before his star took off as Sonny Corleone in "The Godfather," on Wednesday tweeted a picture of Sayers and offered his condolences to the football great's loved ones.
"To one of the greatest ever an inspiration to so many," Caan wrote. "So proud to have known him. My love and condolences to the family."
Sayers, a star at the University of Kansas where he earned the "Kansas Comet" nickname, was voted in to the Hall of Fame in 1977.
Sayers had kept a low profile in recent years, as he fought debilitating dementia.
A clearly weakened Sayers appeared at an event in Chicago last year, marking the 100-year anniversary of the storied franchise.
Fellow Bears legends Mike Singletary and Dick Butkus doted on Sayers and said they were happy to see him that day.
On Wednesday, Butkus paid tribute to his longtime friend and old teammate.
"Will miss a great friend who helped me become the player I became because after practicing and scrimmaging against Gale I knew I could play against anybody,” Butkus said. “We lost one of the best Bears ever and more importantly we lost a great person.”