The flight landed safely after the co-pilot took over the controls and diverted the plane to Syracuse, New York.
A spokesperson said the airline was “incredibly saddened” and was focusing on the pilot’s family and colleagues.
She added that the pilot had appeared ill during the flight, prompting the diversion.
Flight 550 left Phoenix before midnight on Sunday, and landed on Monday morning, the BBC reported.
A new crew was sent to Syracuse to fly the passengers to Boston, where they arrived on Monday early afternoon.
The spokesperson insisted that there was never a question about whether the flight would be able to land safely.
"We’re certainly well qualified to handle situations like these," she said. "That’s why you’ve got more than one pilot in a cockpit."