The president said the law "will set into motion what a generation of Americans have fought for."
He said he was confident the Senate would make fixes to the legislation "swiftly."
The president praised those House members who had "taken their lumps" during the overhaul debate. Shouted one lawmaker in the audience to laughter, "Yes we did!"
Obama paid tribute to what he called the "historic leadership and uncommon courage" of the members of Congress who pushed ahead with the measure amid the often heated debate. He also hailed the new law, saying it helps lift a "decades-long drag" on the economy.
With Victoria Kennedy, widow of the late Sen. Edward Kennedy in the audience, Obama took note of the long battle to bring the health overhaul measure to his desk. "He was confident we would do the right thing," the president said of the longtime Democratic lawmaker.
"We are not a nation that does what's easy ... we are a nation that faces its challenges and faces its responsibilities."
Now, Obama must sell the law's merits to a wary American public.
The next act begins Thursday, when Obama visits Iowa City, Iowa, where he announced his health care plan as a presidential candidate in May 2007. There Obama plans to talk about how the new law will help lower health care costs for small businesses and families, selling the overhaul to Americans who are deeply divided over the plan.