To bid the airline goodbye the company threw a party. Many of the passengers didn't know they were on this historical flight until they got to the airport.
Jim Doyle of Philadelphia says, "Heard about it on my way in, but I didn't know I was on it."
Cynthia Sosnowski of Shamong, New Jersey tells us, "We had no idea this was taking place today. We were just on our way to Florida and we walked into a celebration."
But others booked the trip just for this.
Habib Issa of Los Angeles says, "I'm a plane buff. I'm an employee. I enjoy the aviation business."
Issa has flown around the world twice, and he is taking the entire last trip with US Airways - over 7,000 miles.
Flight 1939, named for the airline's founding year, is on its way to Charlotte, North Carolina. It will also make stops in Phoenix and San Francisco.
13-year-old Ethan Hellofs of Chapel Hill, North Carolina, talked his parents into letting him be a part of the trip. He'll be flying the entire journey as well.
"I don't think that anytime soon there's going to be an opportunity like this," Ethan said. "I just want to be a part of aviation history."
The flight pushed off from the gate one minute early, at 10:04 a.m., and took off at 10:36 a.m.
The Airbus A321 will return to Philadelphia on Saturday under the American Airlines banner, following the completion of a merger announced in 2003.
Meanwhile, residents of Pittsburgh were upset the flight wasn't stopping there. US Airways was formed in Pittsburgh as All American Aviation. It later operated as Allegheny Airlines before becoming USAir.
US Airways dropped Pittsburgh as a hub in 2004 and American Airlines shut down its nearby flight operations control center in August, shifting about 650 jobs to Fort Worth, Texas.