Defying national political headwinds and a nearly deadly health crisis, Lt. Gov. John Fetterman won a narrow victory in Pennsylvania’s key U.S. Senate election, the most expensive of all the nation’s fiercely contested midterm races.

Mr. Fetterman, the highest-profile progressive politician in a politically divided state, declared victory shortly after 1 a.m. Wednesday in his race against celebrity surgeon Mehmet Oz for Pennsylvania’s pivotal U.S. Senate seat. The Associated Press called the race shortly before 2 a.m. The win shifts the national political landscape, giving Democrats new hope for holding onto control of the Senate, which now comes down to neck-and-neck races in Arizona, Georgia, Nevada and Wisconsin.

Less than six months after a stroke nearly killed him, Mr. Fetterman took the stage at his election night celebration at Stage AE on the North Shore to thunderous applause. With just more than 5 million votes counted as of about 2 a.m., Mr. Fetterman led Mr. Oz by more than 110,000 votes — a larger margin than President Joe Biden racked up two years ago when he beat Donald Trump in the state.

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Mr. Fetterman’s victory could offer the Democratic Party a new pathway to assembling a winning coalition in an electorate that’s undergone fundamental shifts since Mr. Trump’s surprise win in the 2016 presidential election. He has long advocated campaigning in deep-red areas full of white, working class voters that have shifted toward the GOP in recent decades, not to win majorities there but to cut in to Republican advantages by splitting their voting coalitions.