Geithner had said he would leave the department after the conclusion of Obama’s first four-year term. The president was sworn in on Sunday for a second term.
Obama has nominated longtime Washington insider Jack Lew, his current chief of staff, to succeed Geithner. His nomination requires Senate approval.
Deputy treasury secretary Neal Wolin is to serve as acting secretary pending Lew’s confirmation.
Geithner, the former head of the Federal Reserve Bank of New York, took the helm at Treasury in 2009. He had a rocky start, but has since emerged as one of the more high-profile people to hold the job in recent years.
His departure comes amid a major reshuffling of Obama’s cabinet for his second term.
Several cabinet heavyweights, including Secretary of State Hillary Clinton and Defence Secretary Leon Panetta, have announced plans to leave the administration.
Also on Tuesday, US Trade Representative Ron Kirk announced he would depart his post in late February.
Under Kirk’s watch, the US signed bilateral trade agreements with South Korea, Colombia and Panama, even as wide-sweeping talks under the World Trade Organization’s Doha round languished.
Kirk announced earlier this month that the US would join a group of 20 trading partners to attempt to negotiate a global agreement on services.
In a statement, Obama praised Kirk for his progress on international talks and for serving as a “tremendous advocate for the American worker” in striving to crack down on unfair trade practices around the world.