"This has been a legislative fight that will be in the record books," Harry Reid, the Democratic senate majority leader, said.
Battle to continue
And the political battle looks set to continue as ruling Democrats and opposition Republicans fight for control of congress in November elections.
Al Jazeera's Rosiland Jordan reports on the US healthcare debate that has turned ugly
Obama, launching a public relations blitz to sell the new programme, mocked his Republican critics and said their promise to make repeal of the law the centrepiece of the congressional campaign would backfire.
"If they want to have that fight, I welcome that fight," Obama said in Iowa, in his first major speech since signing the law on Tuesday.
"I don't believe the American people are going to put the insurance industry back in the driver's seat. We've been there already and we're not going back," he said.
The overhaul of the $2.5 trillion healthcare system is the most dramatic change in US health policy in four decades.
It will extend coverage to an estimated 32 million uninsured Americans
and bar insurance practices such as refusing coverage to those with pre-existing medical conditions.
The final changes approved by congress on Thursday include an expansion of federal subsidies to make insurance more affordable and more state aid for the Medicaid programme for the poor.
They also eliminate a controversial senate deal exempting Nebraska from paying for Medicaid expansion costs, close a gap in prescription drug coverage for seniors and delay a tax on high-cost insurance plans.
The final package also would extend taxes for Medicare, the federal health insurance programme for the elderly, to unearned income.
It also includes reform of the student loan programme.
Republicans have fought the measure as a costly government takeover of healthcare that would restrict patient choice and drive up insurance premiums.
"This has been a sombre week for the American people.
John Boehner the Republican House minority leader, said that Obama had "with the stroke of a pen … signed away another share of Americans' freedom".
But Obama said he would be happy to engage Republicans in a debate over repeal of the law.
"I say go for it," Obama said. "If these congressmen in Washington want to come here to Iowa and tell small business owners that they plan to take away their tax credits and essentially raise their taxes, be my guest."
Tensions over the massive healthcare overhaul continued on Thursday, with Democrats and Republicans disclosing new details of threats against them in the aftermath of the bill's passage and trading blame over the threats and attacks.
At least four Democratic offices in the states of New York, Arizona and Kansas were attacked and at least 10 members of congress have reported threats, including obscene phone messages and a fax bearing the image of a noose, congressional leaders have said.