Mike Tyson seemed to lose his cool on a plane on Wednesday night … repeatedly punching a man in the face after the guy had apparently annoyed him.

TMZ Sports has learned … the incident all went down at around 10:30 PM PT as Tyson was slated to fly out of San Francisco International Airport to Florida.

A witness on the plane says as he and his friend were boarding Tyson’s flight … the boxing legend was initially cool with them and the other passengers.

The witness tells us Mike took a selfie with him … and then was patient with his overly excited buddy, who kept trying to talk to the 55-year-old fighter as he sat behind him.

Eventually, though, we’re told Tyson had enough of the guy behind him talking in his ear … and told him to chill. When the guy didn’t, that’s when the witness says Tyson started to throw several punches at the man’s face.

Video we obtained shows Tyson throwing a flurry of blows at the man, which you can see bloodied the passenger’s forehead. The witness says Mike walked off the plane just seconds later.

We’re told the man who was punched received medical attention and then went to the police over the incident. We’ve reached out to cops for comment, but so far, no word back yet.