The new marketplaces are supposed to work like an Amazon.com for health insurance, providing consumers with one-stop shopping for competitively priced coverage.
"More competition will drive down costs, and exchanges will give individuals and small businesses the same purchasing power big businesses have today," Health and Human Services Kathleen Sebelius said in a statement.
Experts say it's anybody's guess how the national rollout will go. If a state is not ready, the law requires the federal government to step in to run its exchange. But the Obama administration's request for $800 million to operate federal exchanges has gotten a frosty reception from congressional Republicans.
The new markets are for individuals and small businesses buying plans. Most people who now have employer health insurance will not have to make changes. It's a design that works well in Massachusetts, where an exchange has been in place for several years.
Massachusetts achieved political consensus about its health-care overhaul under former GOP Gov. Mitt Romney, who is now seeking his party's presidential nomination. That's far different from the enduring national divisions over President Obama's law, even if it used Romney's as a foundation.
Setting up 50 state exchanges wouldn't be easy even if the federal overhaul enjoyed widespread support.
For things to go smoothly, state and federal officials must work together to verify private personal and financial details for millions of people, make sure that consumers are enrolled in the right health plan, and accurately calculate how much government aid, if any, each household is entitled to.
All that has to get done in hours, not weeks.
Nearly 30 million people are eventually expected to get private health coverage through exchanges, about half of whom are currently uninsured.
Another group of uninsured people - as many as 16 million low-income Americans expected to qualify for Medicaid - could also enter the system through their exchanges.
States are moving in fits and starts to set up the new markets. Many are on the sidelines waiting for the Supreme Court to rule on whether the federal law is constitutional.
Whether that amounts to an unconstitutional expansion of federal power is among the subjects of a showdown that begins March 26, when the high court is set to begin an unusual three days of arguments. A decision is expected by June.
Sebelius says she expects the court to uphold Obama's Affordable Care Act and thinks states will move quickly once the court has ruled.
Reaction to the complex new federal regulation will probably take several days to filter in. The administration says it received nearly 25,000 comments, and some aspects of the rule will remain open for additional comment before they are made final.
States have until Jan. 1, 2013, to obtain federal approval for their exchanges.