Bill faces uncertain prospects in the Senate.

House Republicans repealed most of President Barack Obama’s signature health-insurance law Thursday in a tight vote, handing President Donald Trump his first legislative victory and vindicating GOP leaders who failed twice before to pass a bill. The vote to overhaul the U.S. health insurance system also set up a second showdown, this one in the Senate, where the bill faces difficult prospects and is expected to undergo significant revisions. The 217-213 House vote came more than a month after Speaker Paul Ryan (R., Wis.) was forced to withdraw the bill to avoid its collapse on the House floor. Late lobbying and amendments in the past week allowed House Republicans to finally clear the measure to roll back and replace much of the Affordable Care Act.

On Thursday, Mr. Trump was exuberant after the vote. “It’s going to be an incredible victory when we get it through the Senate,” he said at a news conference in the White House Rose Garden. “Welcome to the beginning of the end of Obamacare,” said Vice President Mike Pence. No Democrats backed the bill, and 20 Republicans, many from political swing districts, voted against it. The passage allows House Republicans to argue that they have delivered on the party’s promise to overturn the ACA but hands Senate Majority Leader Mitch McConnell (R., Ky.) his thorniest political challenge of the new, Republican-controlled government, as the bill heads to an uncertain fate in his chamber.

The bill passed by the House would end the ACA’s mandate that most individuals buy insurance, and that larger employers must offer insurance to their employees. It would dismantle much of the ACA’s taxes and subsidies and replace them with tax credits, largely tied to age, to help people buy insurance if they don’t get it through employers.

The bill would also reduce funding for Medicaid, the health program for low-income and disabled Americans, and halt federal Medicaid reimbursements for one year to Planned Parenthood Federation of America. Many Democrats criticized GOP leaders for rushing the bill to a vote without an updated estimate of its cost and impact on the country’s health coverage—after Republicans had spent years bashing Democrats for their maneuvering to pass the ACA in 2010. “Other than being the height of hypocrisy, it’s surprising that they would do it this way,” said Rep. Juan Vargas (D., Calif.), who predicted his GOP colleagues from California would pay a political price for supporting the bill. “It means a few of them are not going to come back,” he said.

Behind the scenes at the White House, the vote became a top priority for staff after the president made clear in an interview with The Wall Street Journal on April 12 that he wasn’t interested in moving any major legislation before the House approved a health-care bill. After that, Mr. Trump became more engaged, too, White House officials said, and began dialing lawmakers late into the night.

The toughest challenge at that point was drawing support from the House Freedom Caucus, a group of three dozen conservatives who had refused to back the bill in March, saying the bill needed to do more to reduce the cost of premiums and deductibles. White House Chief of Staff Reince Priebus told members of the caucus that they were “killing our party.” “We’re not going to have a party anymore if you guys can’t figure out how to govern,” Mr. Priebus told them.

In the final days, Rep. Billy Long, a Missouri Republican who normally avoids the media spotlight, set off alarms inside the West Wing when he went public with his opposition on Monday. He backed Mr. Trump on the campaign trail in 2015 when few others in the party were willing to do so.

Mr. Trump called Mr. Long again on Tuesday, and he asked the president to support the amendment aimed at providing additional protections for people with pre-existing conditions, who under the bill could face higher premium costs. On Wednesday, Mr. Long and an influential former committee chairman, Mr. Upton, and others visited Mr. Trump in the White House, where they reached a deal on the changes. Other holdouts among the GOP conference then signed on.

Mr. McConnell can lose no more than two of his 52 Republicans to pass the bill, and GOP senators in the centrist and conservative wings have already lodged concerns over the House proposal and are working on changes to it. The Senate is likely to drastically revamp the legislation or come up with its own version. “Today’s vote in the House was an important step,” Mr. McConnell said in a statement Thursday that gave few clues as to when the chamber would consider or change the House bill. “We are now closer to giving our constituents freedom from the increased costs, diminishing choices and broken promises of Obamacare.”

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