The aircraft, an Airbus A320 with 147 passengers and a five-member crew on board, was diverted to Syracuse Hancock International Airport in New York state.
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"Unfortunately, our pilot passed away. We are incredibly saddened by this event, and we are focused on caring for our pilot's family and colleagues," American Airlines said in a statement.
American did not provide any details on the cause of death. Flight 550 left Phoenix, Arizona at 11:55 pm local time and landed in Syracuse at 7:13 am local time.
A replacement crew was sent to Syracuse to shuttle the passengers to Boston.
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