The bill was approved 246-183 and sent to the Senate, where a vote was scheduled late Friday afternoon. That vote was to be held open for hours, waiting for Ohio Democrat Sherrod Brown, who was attending a memorial service for his mother and then flying back to cast the deciding vote.
Senate passage would meet a deadline of sending the bill to Obama before a congressional recess begins next week.
The 1,071 page, 8-inch-thick measure combines $281 billion in tax cuts for individuals and businesses with more than a half-trillion dollars in government spending. The money would go for infrastructure, health care and help for cash-starved state governments, among scores of programs. Seniors would get a $250 bonus Social Security check.
Told that no Republican backed the measure, White House press secretary Robert Gibbs reacted by citing another number: "3.5 million jobs that we look forward to saving or creating."
Seven Democrats voted against the bill.
Republicans said the package won't work because it has too little in tax cuts and spreads too much money around to everyday projects like computer upgrades for federal agencies.
"This legislation falls woefully short," said House GOP Leader John Boehner of Ohio. "With a price tag of more than $1 trillion when you factor in interest, it costs every family almost $10,000 in added debt. This is an act of generational theft that our children and grandchildren will be paying for far into the future."
The final $787 billion measure has been pared back from versions previously debated in order to attract support from three Senate GOP moderates - Susan Collins and Olympia Snowe of Maine and Arlen Specter of Pennsylvania. Their help is essential to meeting a 60-vote threshold in the Senate, required to overcome a Republican objection that the bill adds to the deficit.
The bill originally passed the Senate by a 61-37 tally, but Sen. Edward Kennedy, D-Mass., suffering from brain cancer, is not expected to vote this time.
Sen. Judd Gregg, R-N.H., who withdrew his nomination to be Obama's Commerce secretary, said he would vote against the bill.
Democrats lavished praise on the measure, which combines tax cuts for workers and businesses with more than a half-trillion dollars in government spending aimed at boosting economic demand.
"By investing in new jobs, in science and innovation, in energy, in education ... we are investing in the American people, which is the best guarantee of the success of our nation," said House Speaker Nancy Pelosi, D-Calif.
The plan is the signature initiative of the fledgling Obama administration, which is betting that combining tax cuts of $400 a year for individuals and $800 for couples with an infusion of spending for unemployment assistance, $250 payments to people on Social Security, and extra money for states to help with the Medicaid health program for the poor and disabled will arrest the economy's fall.
Local school districts would receive $70 billion in additional funding for K-12 programs and special education and to prevent cutbacks and layoffs and repair crumbling schools. There's about $50 billion for energy programs, much of which goes to efficiency programs and renewable energy.
Some $46 billion would go to transportation projects, not enough to please many lawmakers.
Negotiators insisted on including a $70 billion tax break to make sure middle- to upper-income taxpayers won't get hit by the alternative minimum tax and forced a reduction of Obama's signature tax break for 95 percent of workers.
The AMT was designed 40 years ago to make sure wealthy people pay at least some tax, but is updated for inflation each year to avoid tax increases averaging $2,300 a year. Fixing the annual problems now allows lawmakers to avoid difficult battles down the road, but economists say the move won't do much to lift the economy.
Republicans pointed out a bevy of questionable spending items that made the final cut in House-Senate negotiations, including money to replace computers at federal agencies, inspect canals, and issue coupons for convertor boxes to help people watch TV when the changeover to digital signals occurs this summer.
"This measure is not bipartisan. It contains much that is not stimulative," said Sen. John McCain, R-Ariz., Obama's rival for the White House. "And is nothing short - nothing short - of generational theft" since it burdens future generations with so much debt, he added.