Pitbull will be the program's first host since comedian Jimmy Kimmel in 2008.
The rapper will also perform his new hit single "Timber" with Ke$ha. They join previously announced artists Luke Bryan, Miley Cyrus, Florida Georgia Line, Lady Gaga, Imagine Dragons, Kendrick Lamar, Macklemore & Ryan Lewis, and One Direction.
Additional acts and presenters will be announced in the coming weeks, ABC said.
"I am truly honored to be hosting the 2013 American Music Awards," Pitbull, whose real name is Armando Christian Perez, said in a statement.
"The night is only about one thing, fun! So buckle and get ready. Dale!," he said, using the Spanish slang for "Let's do this!"
"Pitbull is a multi-talented, global superstar and the right man to take the reins of the night, which is going to be one great party," said the American Music Awards' long-time producer Larry Klein. "That's why he is called Mr. Worldwide. He's the perfect choice to celebrate the universal language of music."
The show is to be televised Nov. 24 on ABC from the NOKIA Theatre L.A. LIVE.