Mackey, who also served as the first president of the National Football League Players Association, died Wednesday in Baltimore after a 10-year battle with frontal temporal dementia, The Baltimore Sun reported.
"John Mackey is still our leader. As the President of the NFL Players Association, he led the fight for fairness with a brilliance and ferocious drive," said DeMaurice Smith, executive director of the NFLPA. "His passion continues to define our organization and inspire our players. His unwavering loyalty to our mission and his exemplary courage will never be forgotten."
In his nine seasons with the Colts, the team won a Super Bowl and three conference championships.
Don Shula, the Colts' coach from 1963 to 1969, said Mackey revolutionized the position of tight end.
"Previous to John, tight ends were big strong guys like [Mike] Ditka and [Ron] Kramer who would block and catch short passes over the middle," Shula said. "Mackey gave us a tight end who weighed 230, ran a 4.6 and could catch the bomb. It was a weapon other teams didn't have. "
Inducted into the Hall of Fame in 1992, Mackey caught 331 career passes for 5,236 yards and 38 touchdowns.
Mackey is survived by his wife, Sylvia, a son, two daughters and six grandchildren.