Tyson discussed the cross-generational dream matchup with Yahoo Sports.
"I know it's a fantasy game," he said.
"Most likely I would win the fantasy, but I wouldn't win the real fight. Ali's the greatest there's ever been."
The World Boxing Super Series held a simulation in late March featuring eight of the best heavyweight fighters in boxing history. Tyson defeated Ali in the championship fight by judges' decision.
Iron Mike has always held The Greatest, who died in June 2016 at the age of 74, in high regard.
"He'll fight you to the end. He's really game, like a pitbull or a f--king rooster," Tyson told Clay Skipper of GQ in 2016.
"But he looked like a model in his prime! He looked more like a model than a fighter. He was just a dead-game guy. He was dead game. He had too much pride. He refused to lose."
The former undisputed heavyweight champion added: "Ali is the most competitive fighter ever."
A lot of the same attributes can be applied to Tyson, who started his career with 37 consecutive victories and held a 50-4 record before dropping his final two bouts at age 38. He retired in 2005.
BoxRec's rankings place Ali as the second-best heavyweight in history behind only Joe Louis. Tyson is ninth on the all-time list.
At his peak, however, there's little doubt Kid Dynamite could have given any heavyweight in history a legitimate challenge, including Ali.