IMS president Doug Boles stated on Friday that Unser had "died peacefully in his beloved Chama [New Mexico, ed.] home after a 17-year battle with Cancer."
As part of the Unser dynasty, "Big Al" was a fixture at the Indy 500 for three decades, his 27 starts the third highest number of appearances in history.
He was extremely successful, too, being one of four drivers to join the elite club of four-time winners, which also includes A.J. Foyt, Rick Mears and - since this year - Helio Castroneves.
Unser won the great race in 1970, 1971, 1978 and 1987, his fourth win making him the oldest-ever winner at 47. It was a race he famously only entered at the last minute as a stand-in for the injured Danny Ongais, Penske pressing into action a March-Cosworth that had been sitting on display as a show car.
The Albuquerque, New Mexico native led an all-time high of 644 laps at the Speedway.
Unser's IndyCar career, which started in 1964, also includes 39 race wins and three championships. He took the USAC title in 1970 after taking 10 wins out of 18 races across its diverse paved oval, road course and dirt oval schedule. He later won the IndyCar title twice in 1983 and 1985.
Unser followed in the footsteps of his eldest brother Jerry, who raced in the 1958 Indy 500 but was killed in a practice crash the following year.
He retired ahead of the 1994 Indy 500, when at age 54 he failed to qualify with an underfunded Arizona Motorsports entry. His son Al Unser Jr. would go on to win the race that year.
Unser was inducted into the Indianapolis Motor Speedway Hall of Fame in 1986 and the International Motorsports Hall of Fame in 1998.
The news of Unser's passing comes after a true annus horribilis for the Unser dynasty. Unser's elder brother Bobby, himself a three-time winner at Indianapolis and one of the sport's most colourful characters, passed away in May this year aged 87.
Bobby's son and Al's nephew Bobby Unser Jr. died six weeks later at the age of 65.
IMS president Boles said Unser "achieved his successes competing against many of the best our sport has ever seen, which makes his accomplishments on the track even more impressive.
"Al's combination of his quiet and humble approach outside the car with his fierce competitive spirit and fearless talent behind the wheel, made him a fan favourite.
"He will be remembered as one of the best to ever race at Indianapolis and we will all miss his smile, sense of humor, and his warm, approachable personality.
"Our thought and prayers are with [wife] Susan Unser, the entire Unser family, and all Al's friends and fans."