Stern spent 14 years heading the 2.2-million member union that he helped build into one of the nation's largest and most politically active.
His resignation two years before his term ends surprised many in the labor and political worlds.
Stern wielded more clout than ever as Democrats control the White House and Congress.
Stern does not specify why he's leaving. He says in a video statement on his union's Web site that there is "a time to learn, a time to lead, and a time to leave."
Union Secretary-Treasurer Anna Burger will replace Stern until the board elects a new president.