The agreement, passed by a 298-117 vote, will now head to the Senate for its vote, but it was unclear if it would be passed before Congress adjourns ahead of the November 4 elections.
Signed by President George W. Bush and Indian Prime Minister Manmohan Singh in July 2005, the deal offers India access to Western technology and cheap atomic energy provided it allows UN nuclear inspections of some of its nuclear facilities.
Bush on Saturday congratulated the House on the vote.
"The passage of this legislation by the House is another major step forward in achieving the transformation of the US-India relationship," he said, urging Senate now to adopt the bill.
But the deal has faced criticism from opponents who argue that India, which first tested an atomic weapon in 1974, is not a signatory of the nuclear Non-Proliferation Treaty (NPT).