The vote sent the bill to the Senate, where debate is expected to begin as early as this week on a companion measure already taking shape. Democratic leaders have pledged to have legislation ready for Mr. Obama's signature by mid-February.
"This recovery plan will save or create more than three million new jobs over the next few years," the president said in a written statement released after the House voted.
Mr. Obama meet with Republican lawmakers Tuesday, hoping to shore up bipartisan support for the bill. House Minority Leader John Boehner of Ohio said Wednesday on "Good Morning America" that Republicans were still concerned about some of the spending that "has nothing to do with creating jobs or preserving jobs."
After speaking with the president, Indiana Rep. Mike Pence, the No. 3 Republican in the House, criticized the bill saying, "The only thing it will stimulate is more government and more debt. And the president heard that message today."
But Speaker Nancy Pelosi said Tuesday's events signaled the start of a new era, the Associated Press reported. "The ship of state is difficult to turn," Pelosi said. "But that is what we must do. That is what President Obama called us to do in his inaugural address."
Even if voting falls along partisan lines Wednesday, the House is expected to pass the bill with a comfortable majority. President Obama had sought to unite the parties behind the plan as the first move in kickstarting the economy from recession and addressing rising unemployment.
The House measure includes about $544 billion in spending and about $275 billion in tax cuts, media organizations report. Much of the spending would go to health care, jobless benefits, food stamps and other programs that would benefit families directly affected by the downturn.
Former Vice President Al Gore also appeared on Capitol Hill Wednesday in support of the measure and to testify about global climate change.
In prepared remarks, Gore wrote, "[E]ntrenched interests in Washington will be working hard to weaken the legislation -- opposing funding for clean energy programs that support things like wind, solar, energy efficiency and a new national electric grid," Politico reported. "Today, we can start to get America back on track."
During debate on the bill Tuesday, Republicans cited concerns over inadequate tax relief for small businesses and criticized some of the spending plans as wasteful. Democrats made one change, voting to delete $20 million for renovations to the National Mall, a project that had come under fire as frivolous.
Senate committees were working on a separate version of the measure and leaders from both houses have promised to have the measure to the President by mid-February.
On Tuesday, the Senate Appropriations Committee voted 21-9 to support a $366 billion spending portion of the plan.