The president clinched a landmark nuclear deal with India and assurances from Pakistan that it will not waver in the US-led "war on terror" during his maiden visit to South Asia.
Mr Bush and Indian Prime Minister Manmohan Singh sealed what they hailed as an "historic" nuclear deal that aims to lift three-decade-old US restrictions on sharing civilian nuclear technology with India.
The nuclear agreement places 14 of India's 22 nuclear power reactors under international safeguards.
It was the highlight of Bush's three-day trip to India which also included brief visits to Afghanistan and Pakistan.
"By working with these leaders and the people of these three nations, we're seizing the opportunities this new century offers and helping to lay the foundations of peace and prosperity for generations to come," the president said in his weekly radio address to Americans.
But the Bush administration needs approval from the US Congress and the 45-nation Nuclear Suppliers Group in order to share American civilian nuclear technology with the booming Asian giant.
The deal faces bipartisan opposition, with several lawmakers wary and some, like Democratic Representative Ed Markey, even vowing to block it outright, saying it has "blown a hole" in the world's nuclear rules.
Several Republican lawmakers, meanwhile, praised the civil nuclear energy agreement as a milestone in improving relations with India.