Defying the odds in heavily pro-Trump West Virginia, Democratic incumbent Sen. Joe Manchin III won re-election Tuesday, defeating Republican Patrick Morrisey and dashing the GOP’s hopes of snatching a Senate seat in one of the reddest states in the nation.

With about 57 percent of the vote counted, networks called the race just after 9 p.m. Mr. Manchin had 51 percent, compared to 44 percent for Mr. Morrisey, the state’s attorney general.

The victory ensures a second term in the Senate for Mr. Manchin, the state’s former governor and widely considered the most conservative Democrat in the chamber. Unlike most others in his party, Mr. Manchin has shied away from harsh criticism of Mr. Trump, who won the state by more than 40 percentage points in the 2016 presidential election and remains wildly popular there.

Mr. Manchin was the only Democrat to back the president’s pick for the U.S. Supreme Court, Justice Brett M. Kavanaugh, who faced multiple accounts of sexual misconduct.

The incumbent senator even sent out campaign mailers during the final weeks of the election stressing that he “supports Trump when he’s right,” and he touted his bipartisanship by writing at least five op-eds in recent months with Republican colleagues in the Senate on issues ranging from opioids to Obamacare.

But that didn’t stop the president and his allies from making Mr. Manchin a top target. Mr. Trump visited the state multiple times this year, including a late rally with Mr. Morrisey in Huntington on Friday. Vice President Mike Pence, Donald Trump Jr., and other high-profile Republicans also stumped for the attorney general.

Mr. Morrisey tied himself closely to the president throughout the race, painting Mr. Manchin as a “dishonest Washington liberal” who would undermine Mr. Trump’s agenda if given a second term.

Outside of Mr. Trump, the race centered on the opioid epidemic that has ravaged West Virginia. Mr. Morrisey bashed Mr. Manchin for not doing enough to address the crisis, while the incumbent senator countered by attacking the attorney general’s time in Washington as a lobbyist for the pharmaceutical industry.

Republicans long had seen West Virginia as a prime target in this year’s Senate contests. Mr. Morrisey last spring came out on top of a six-man primary field, fending off the most serious challenges from Rep. Evan Jenkins and former coal company CEO and ex-convict Don Blankenship.

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