House Democrats approved the most dramatic health policy changes in four decades by 219 to 212 votes.
The vote sends the bill, already passed by the Senate, to President Obama to sign into law.
The overhaul will extend health coverage to 32 million Americans, expand the government health plan for the poor, impose new taxes on the wealthy and bar insurance practices such as refusing to cover people with pre-existing medical conditions.
The vote capped a year-long political battle with Republicans that consumed the US Congress and dented Mr Obama's approval ratings, and fulfilled a goal that had eluded many presidents for a century - most recently Democrat Bill Clinton in 1994.
'Tonight, at a time when the pundits said it was no longer possible, we rose above the weight of our politics,' President Obama said during a late-night appearance at the White House.
'This legislation will not fix everything that ails our healthcare system, but it moves us decisively in the right direction. This is what change looks like,' he said.
House Democrats hugged and cheered in celebration as their vote count hit the magic number of 216, and chanted: 'Yes we can.'
Every Republican opposed the bill, and 34 Democrats joined them in voting against it.
Republican and industry critics claimed the $940bn bill was a heavy-handed intrusion in the healthcare sector that would drive up costs, increase the budget deficit and reduce patients' choices.
Both parties geared up for another battle over the healthcare bill in the campaign leading up to November's congressional elections, and opponents across the country promised to challenge the legislation on the state level.
Big Changes
The healthcare revamp, President Obama's top domestic priority, will usher in the biggest changes in the $2.5 trillion US healthcare system since the 1965 creation of the government-run Medicare health program for the elderly and disabled.
It will require most US citizens to have health coverage, give subsidies to help lower-income workers pay for coverage and create state-based exchanges where the uninsured can compare and shop for plans.
Major provisions such as the exchanges and subsidies will not kick in until 2014. However, many of the insurance reforms, such as barring companies from dropping coverage for the sick, will begin in the first year.
House Democrats also approved a package of changes to the Senate bill late last night. The Senate will take up that package this week under budget reconciliation rules requiring a simple majority to pass.
The changes include elimination of a controversial Senate deal exempting Nebraska from paying for Medicaid expansion costs, the closure of a gap in prescription drug coverage and modifications to a tax on high-cost insurance plans.
Republicans said they would challenge those changes in the Senate through parliamentary points of order.
'Senate Republicans will now do everything in our power to replace the massive tax hikes, Medicare cuts and mandates with the reforms our constituents have been calling for throughout this debate,' Senate Republican leader Mitch McConnell said.
The vote on the overhaul followed days of heavy lobbying of undecided House Democrats by Mr Obama and House leaders.
The narrow victory was clinched earlier yesterday by a deal designed to appease a handful of Democratic opponents of abortion rights.
Under the deal, Mr Obama will issue an executive order affirming government restrictions on the use of federal funds for abortion would not be changed by the healthcare bill.
The health insurance industry has vigorously opposed the overhaul, but insurance stocks rallied late last week as investors began to realise their worst fears had not materialised.
Pharmaceutical companies, hospitals and others will benefit from more insured patients, and the bill does not allow the government to cap prices and premiums, which would have hurt pharmaceutical companies and insurers.
Opinion polls show the public also has a mixed view.
The bill's final approval represented a stunning turnaround from January, when it was considered dead after Democrats lost their crucial 60th Senate vote in a special Massachusetts Senate election.
But Mr Obama and Democrats rallied last month for a final push, and will use the Senate's budget reconciliation rules to bypass the need for 60 votes on the changes they sought to the overhaul.
