The Republican Party seized control of the U.S. Senate Tuesday night, dealing a significant blow to Democratic hopes of maintaining their slim majority in the upper chamber.

The decisive moment came in Nebraska, where veteran Republican Senator Deb Fischer fended off an unexpectedly strong challenge from independent candidate Dan Osborn. In Ohio, political newcomer Bernie Moreno, a Colombian-born businessman backed by Donald Trump, unseated three-term Democratic Senator Sherrod Brown in the cycle’s most expensive race, which saw nearly $400 million in campaign spending.

Meanwhile, West Virginia Governor Jim Justice claimed the seat of retiring Democratic Senator Joe Manchin.

Democratic efforts to unseat high-profile Republican incumbents Ted Cruz in Texas and Rick Scott in Florida fell short, despite aggressive campaigns that focused heavily on reproductive rights and healthcare access. With the GOP now holding 51 seats, Democrats face [removed “now”] an uphill battle in remaining contests across Pennsylvania, Michigan, and Wisconsin, where they’re fighting to prevent a broader Republican sweep.

It remains to be seen whether South Dakota Senator John Thune or Texas Senator John Cornyn will succeed Mitch McConnell as Republican Senate leader. Both veteran lawmakers, who previously served in top party positions, will face off in next week’s closed-door leadership vote that could reshape President-elect Donald Trump’s vision for the future of the country.