The deal ratified Friday was approved by 74 percent of the pilots.
The pact, which includes pay raises, gives the union a 13.5 percent stake in the company but allows American to outsource flights to regional carriers and partners, the Chicago Tribune reported Saturday.
The contract could clear the way for AMR, American's parent, to merge with US Airways.
"Today's ratification gives us the certainty we need for American to successfully restructure, providing opportunity and growth for all of our people and stakeholders," American Airlines Senior Vice President of People Denise Lynn said in a statement.
The pilots union was the last to reach a contract with American. Pilots had been flying without an agreement since 2006.