Democrats currently control 59 seats in the senate, and they need to win over at least one Republican vote to overcome delaying tactics that could kill the bill.
The main disagreement centres on measures to address troubled financial institutions without resorting to costly taxpayer-funded bail-outs.
Appearing on the Fox News network on Sunday, Mitch McConnell, the Republican senate minority leader, said he would work to halt the beginning of debate on the bill, saying he was confident that all 41 Republican votes would be cast in favour of a delay.
McConnell said a proposed $50bn fund as part of the legislation to wind down failing firms would lead to endless bail-outs – a charge the Obama administration has repeatedly denied.
|Obama has said his financial reforms would bring an end to taxpayer bail-outs [AFP]
"It's better not to pre-fund, no matter how you fund it, whether it's a tax on banks or whatever it is, a fund that creates expectation it will be used," McConnell said.
"What we need to do is make it virtually, if not impossible, to be too big to fail."
The legislation would bring with it the most sweeping overhaul of the US financial system in decades.
Its main aim is to tighten government oversight of financial firms, with a view to preventing another Wall Street meltdown like the one in 2008 that triggered the recession.
The proposed consumer protection agency would also help fight loan and mortgage abuse, and it would give the government new powers to seize and dismantle huge financial firms on the brink of failure if their collapse threatens the economy.
That is opposed by many Republicans, who say it leaves the door open to big government bail-outs in the future.
Austan Goolsbee, the White House economic adviser, said the changes would end bail-outs and "hold accountable the people that get into the messes, so if they get in trouble, they fail".
The bill, he said, would bring with it "the strongest consumer protections ever in this country".
Last week Obama travelled to Wall Street to urge what he called the "titans of industry" to back regulatory reform and support the new legislation.
He also cautioned against any efforts to undermine moves to tighten regulation of derivatives, the complex and risky financial instruments seen as a crucial factor in triggering the 2008 crisis.
"It is essential that we learn the lessons of this crisis, so we don't doom ourselves to repeat them," Obama said.
"Make no mistake, that is exactly what will happen if we allow this moment to pass."