He appealed to members of parliament and assured them that the nuclear agreement was done "in the best interests of our people".
The government will need a simple majority of votes, but opposition parties, including the Bharatiya Janata Party (BJP), a Hindu nationalist party, are equally confident.
"The government is today like a patient in an intensive care unit. The first question naturally asked is, 'is he going to survive or not?'" said Lal Krishna Advani, the BJP leader.
If a vote of no-confidence is levelled against the Congress-led coalition, early elections will be announced and must be held within six months.
The stakes are so high that the government has reportedly released six members of parliament, currently serving jail terms, to vote.
India tested nuclear weapons in 1974 and 1998 and refuses to sign the nuclear Non-Proliferation Treaty, and is currently barred from buying nuclear technology and fuel.
The deal would allow such purchases but subject India's civilian nuclear sites to international controls such as UN inspections, said to ensure that any purchases are not diverted for military use.
Opponents say the deal will compromise India's position as a politically neutral country, and that the requisite UN inspections would limit the country's ability to develop its weapons programme and deter Pakistan, its main regional rival.
They also argue that there are strings attached, and doing a deal with the US would undermine its freedom to buy oil and gas from countries such as Iran, or shop for armaments with traditional suppliers including Russia.
The communists and the BJP are also trying to widen the terms of the debate.
They have been speaking out against rising food and fuel prices - inflation is currently around 12 per cent - and arguing that hundreds of millions of the poorest people have been left behind in India's economic boom.
But the core issue is the nuclear deal - a topic spanning India's energy security as well as its place in the world.
Advani told parliament: "We are not against nuclear energy. We are not against a very close relationship with America. But we would never like India to become party to an agreement which is unequal.
"This deal makes us a subservient partner. It makes India a junior partner."