Washington (CNN) -- A federal judge in Florida has tossed out the sweeping health care reform law championed by President Barack Obama, setting up what is likely to be a contentious Supreme Court challenge over the legislation in coming months.

Monday's sweeping ruling came in the most closely watched of the two dozen separate challenges to the law. Florida along with 25 states had filed a lawsuit last spring, seeking to dismiss a law critics had labeled "Obamacare."

U.S. District Judge Robert Vinson declared unconstitutional the key provision of the Patient Protection and Affordable Care Act -- the so-called "individual mandate" requiring most Americans to buy health insurance by 2014 or face penalties. Vinson also declared unconstitutional the section of the act that withholds Medicare funds from states that refuse to participate.

But unlike another federal judge who ruled the individual mandate unconstitutional last month, Vinson ruled that the unconstitutionality voided the entire act.

"I must reluctantly conclude that Congress exceeded the bounds of its authority in passing the Act with the individual mandate. That is not to say, of course, that Congress is without power to address the problems and inequities in our health care system," wrote Vinson.

"Because the individual mandate is unconstitutional and not severable, the entire Act must be declared void. This has been a difficult decision to reach, and I am aware that it will have indeterminable implications," Vinson wrote, adding, "At a time when there is virtually unanimous agreement that health care reform is needed in this country, it is hard to invalidate and strike down a statute titled "The Patient Protection and Affordable Care Act."

The Justice Department declared its intentions to appeal the ruling to the 11th Circuit Court of Appeals.

"We strongly disagree with the court's ruling today and continue to believe -- as other federal courts have found -- that the Affordable Care Act is constitutional," said department spokeswoman Tracy Schmaler.

"This is one of a number of cases pending before courts around the country, including several that the government has won in the district courts that are now before the courts of appeals. There is clear and well-established legal precedent that Congress acted within its constitutional authority in passing this law and we are confident that we will ultimately prevail on appeal."

Schmaler added that the department is determining what other steps to take "including seeking a stay ... while the appeal is pending to continue our progress toward ensuring that Americans do not lose out on the important protections this law provides, that the millions of children and adults who depend on Medicaid programs receive the care the law requires, and that the millions of seniors on Medicare receive the benefits they need."

Sen. Marco Rubio, the Republican freshman senator from Florida, praised the ruling and called on the Senate to take up the recently approved House bill repealing the act.

"ObamaCare was a mistake," he said. "However, we cannot leave this decision in the hands of judges alone. The Senate Democrat leadership should follow the House's lead and hold an up-or-down vote to repeal ObamaCare. The optimal outcome for Florida and the American people is to repeal the federal health care law and replace it with common-sense reforms that will lower health care costs and get more Americans insured."

House Speaker John Boehner, R-Ohio, agreed that the Senate should take up the repeal bill, saying it was "the easiest way to protect the American people."

"Today's decision affirms the view, held by most of the states and a majority of the American people, that the federal government should not be in the business of forcing you to buy health insurance and punishing you if you don't," he said. "It's not only unconstitutional, it's also unaffordable. This health care law remains a major source of uncertainty for small businesses, which is why all parties involved should request that this case be sent to the U.S. Supreme Court for a swift and fair resolution."

Newly elected Republican National Committee Chairman Reince Priebus joined the call for the Senate to vote on repeal -- after Senate Republicans noted earlier in the day that all of them would vote in favor.

"The new Republican House majority has already fulfilled its promise to the American people and voted to repeal this unaffordable, unconstitutional legislation and it is time for the Senate to follow suit," he said. "Senate Democrats cannot continue to defend the indefensible and keep a law on the books that is not only opposed by the American people but also raises clear constitutional concerns."

Senate Majority Leader Harry Reid of Nevada, however, disagreed that Americans want the act repealed.

"This lawsuit is nothing more than an attempt by those who want to raise taxes on small businesses, increase prescription prices for seniors and allow insurance companies to once again deny sick children medical care," he said. "Health care reform is the law of the land and, now that Americans see its benefits, a majority of them oppose Republicans' dangerous plans to repeal a law that put patients in control of their own health care. Rather than focusing obsessively on the past and pushing a plan that will add $1 trillion to the deficit, Republicans should join Democrats in working to create jobs and strengthen the middle class."

And Rep. Pete Stark, D-California, and ranking member of the House Ways and Means Committee, pointed out that Vinson's 78-page ruling went against several other district court rulings.

"Republicans have no problems with activist judges as long as they're taking rights away from the American people," he said. "Several other judges across the country have ruled that health reform is clearly constitutional, a viewpoint that will win the day at the end of all this partisan posturing."

The states bringing suit in this appeal are Alabama, Alaska, Arizona, Colorado, Florida, Georgia, Idaho, Indiana, Iowa, Kansas, Louisiana, Maine, Michigan, Mississippi, Nebraska, Nevada, North Dakota, Ohio, Pennsylvania, South Carolina, South Dakota, Texas, Utah, Washington, Wisconsin, and Wyoming.

Virginia and Oklahoma have filed separate challenges, along with other groups and individuals opposed to the law.

A federal judge in eastern Virginia has also found the health care law unconstitutional, while two other federal judges, one in western Virginia and one in Michigan, have ruled just the opposite. Additionally, according to the White House, 12 other federal judges have dismissed challenges to the law.

The two judges who ruled against the law were appointed by Republican presidents; the two who ruled in favor of the law were appointed by Democratic presidents.

Such disagreements almost ensure the high court will take up the issue. The various cases will likely have to go separate federal appeals courts before the justices would take up one or more of the cases.

There was no indication when the Supreme Court would take the case, although it could be as soon as later this year.

In the Florida case, opponents were targeting not only that individual mandate, but also the law's requirement that each state expand Medicaid to cover more of the low-income uninsured.

"It's an enormous burden on the states that they never agreed to," then-Florida Attorney General Bill McCollum said last month after oral arguments. The Medicaid expansion, he said, amounts to "the compulsion and coercion of the states, in violation of the 10th Amendment."

Under the law, the federal government is supposed to pay states for most of the cost of the Medicaid expansion -- an estimated 95 percent over the first five years, according to an analysis by the Kaiser Family Foundation. However, Texas Attorney General Greg Abbott estimated the expansion could cost his state up to $25 billion over 10 years.

In his ruling Vinson seemed almost apologetic that he had to rule against the government on an issue he repeatedly referred to as monumental. But he said forcing Americans to buy a product like health care insurance that they may not want or need clearly violates the Constitution.

"I will simply observe, once again, that my conclusion in this case is based on an application of the Commerce Clause law as it exists pursuant to the Supreme Court's current interpretation and definition," he wrote. "Only the Supreme Court (or a Constitutional amendment) can expand that."

President Barack Obama has said the requirement is justified for the overall good.

"All we've said is, everybody has to get some basic insurance, so that we're not paying for you when you get sick," he said in an interview last month. "It's the right thing to do, and I'm confident that the courts will uphold it."

The mandate on individuals to buy insurance is not scheduled to go into effect until 2014. But if that portion of the law is ultimately struck down, analysts say it would make it difficult to pay for the law's other, more popular provisions.

In the meantime, the public will already benefit from several other provisions of the law, according to White House health care policy director Nancy-Ann DeParle. Those include requirements that insurers offer coverage to children of beneficiaries until age 26, not deny coverage for pre-existing conditions and not place a lifetime cap on benefits.

The case is Florida v. U.S. Department of Health and Human Services (3:10-cv-91-RV/EMT).