A fourth panel, in Richmond, Virginia, put its decision off until penalties for failing to have health insurance take effect in 2014.
The act passed Congress along strictly partisan lines in March 2010, after a lengthy and heated debate marked by intense opposition from the health insurance industry and conservative groups.
When Obama signed the legislation later that month, he called it historic and said it marked a "new season in America."
While it was not the comprehensive national health care system liberals initially sought, supporters said the law would reduce health care costs, expand coverage and protect consumers.
In place of creating a national health system, the law banned insurance companies from denying coverage to people with pre-existing conditions, barred insurers from setting a dollar limit on health coverage payouts, and required them to cover preventative care at no additional cost to consumers.
It also required individuals to have health insurance, either through their employers or a state-sponsored exchange, or face a fine beginning in 2014.
Supporters argued the individual mandate is critical to the success of the legislation, because it expands the pool of people paying for insurance and ensures that healthy people do not opt out of having insurance until they needed it.
Critics say the provision gives the government too much power over what they say should be a personal economic decision.
Twenty-six states, led by Florida, went to court to say individuals cannot be forced to have insurance, a "product" they may neither want nor need. And they argued that if that provision is unconstitutional, the entire law must go.
The Justice Department countered that since every American will need medical care at some point in their lives, individuals do not "choose" whether to participate in the health care market.
The partisan debate around such a sweeping piece of legislation has encompassed almost every traditional hot-button topic: abortion and contraception funding, state and individual rights, federal deficits, end-of-life care, and the overall economy.
During arguments on March 27, Justice Anthony Kennedy said the law appeared to "change the relationship between the government and the individual in a profound way."
Chief Justice John Roberts argued that "all bets are off" when it comes to federal government authority if Congress was found to have the authority to regulate health care in the name of commerce.
Liberal justices, however, argued people who don't pay into the health system by purchasing insurance make care more expensive for everyone.
"It is not your free choice" to stay out of the market for life, Justice Ruth Bader Ginsburg said during arguments.
"I think the justices probably came into the argument with their minds made up. They had hundreds of briefs and months to study them," said Thomas Goldstein, publisher of SCOTUSblog.com and a prominent Washington attorney, though he conceded that "the oral arguments (in March) might have changed their minds around the margin."
The legislation signed by Obama stretched to 2,700 pages, nine major sections and some 450 provisions.
The first lawsuits challenging the health care overhaul began just hours after the president signed the measure.