A flight attendant, who was formerly a nurse, tried to revive the pilot, but to no avail.
The 147 passengers on board reported feeling a little turbulence, after a sharp drop and an announcement from the co-pilot that the captain was "feeling unwell," according to CBS News.
"Syracuse, American 550, medical emergency, captain is incapacitated, request handling for runway," the co-pilot's radio transmission transcript read.
Airline spokeswoman Michelle Mohr said in a statement that passengers were transferred "without incident" to their final destination.
"We also took care of our customers and sent a replacement crew to [Syracuse] to get them to Boston," the statement read.
The plane landed safely at 7:13 AM ET in Syracuse, New York, and a replacement crew flew them to Boston's Logan Airport, where they arrived at 12:30 PM.
"Unfortunately, our captain passed away," Mohr's statement read. "We are incredibly saddened by this event, and we are focused on caring for his family and our colleagues."
It's the first case of an American Airlines pilot death in mid-flight, but evidently not the first time such a thing has happened in US air travel history.
Last month American Airlines “screwed up“ when the company sent a plane to Hawaii from Los Angeles that was uncertified to fly over water for long distances.