The Senate on Thursday approved former CIA Director Mike Pompeo to be the nation’s next secretary of state, overcoming heavy resistance once again from Democrats to a top Trump nominee.

The vote puts an energetic new manager with a strong rapport with the boss in charge of the demoralized State Department, which has often found itself sidelined in recent months at a time when mounting crises in hot spots such as Iran, Syria and North Korea are confronting the administration.

The 57-42 vote was the second straight strongly partisan vote for a secretary of state, which until President Trump took office usually featured large bipartisan majorities in favor of the president’s choice. Rex W. Tillerson, whom Mr. Trump fired from the job earlier this year, was confirmed last year with 43 “no” votes, all from Democrats.

But on a day when President Trump’s nominee to head the Department of Veterans Affairs, White House physician Dr. Ronny Jackson, withdrew his name from consideration, the confirmation of Mr. Pompeo marked a major personnel win for the administration.

Mr. Pompeo appears determined to hit the ground running, leaving just hours after being sworn in by Supreme Court Justice Samuel A. Alito Jr. for Andrews Air Force Base for a flight to Brussels to meet with top NATO officials.

State Department employees, rocked by morale problems, budget cuts and a disruptive management reorganization that consumed much of Mr. Tillerson’s brief tenure, gave the new boss a round of applause as he boarded the plane, The Associated Press reported. Mr. Pompeo responded with a casual, “Hi, I’m Mike.”

The State Department announced that the new secretary will travel on to Saudi Arabia, Jordan and Israel over the weekend. The Syrian civil war and the Iran nuclear deal are expected to be top topics at each capital. Mr. Pompeo will meet with Saudi King Salman, Israeli Prime Minister Benjamin Netanyahu and Jordanian King Abdullah on the trip, said State Department spokeswoman Heather Nauert.

Shortly after the Pompeo vote, the Senate moved on another long-stalled nomination, approving former U.N. spokesman Richard Grenell to be ambassador to Germany, again with more than 40 Democrats opposed. Mr. Grenell was confirmed to the Berlin post just a day before German Chancellor Angela Merkel arrives for talks with Mr. Trump at the White House.

Mr. Pompeo, a West Point and Harvard Law School graduate and former Republican congressman from Kansas, won high marks for his management of the CIA and for forging a close bond with President Trump that Mr. Tillerson never enjoyed. He carried out a sensitive diplomatic mission for Mr. Trump while awaiting confirmation by meeting secretly with North Korean leader Kim Jong-un this month to prepare the ground for the president’s planned summit in the coming weeks.

“Having a patriot of Mike’s immense talent, energy, and intellect leading the Department of State will be an incredible asset for our country at this critical time in history,” Mr. Trump said in a statement after the vote. “He will always put the interests of America first. He has my trust.”

But Senate Democrats, even some who backed Mr. Pompeo for the CIA a year ago, cited his past hawkish views and his stands on social issues such as same-sex marriage to argue that he did not deserve to be the nation’s top diplomat.

The president’s personal lobbying helped head off an embarrassing rejection of the nominee in the Senate Foreign Relations Committee this week. He persuaded libertarian Sen. Rand Paul, Kentucky Republican, to switch his vote at the last minute and back Mr. Pompeo.

Mr. Paul said he switched in part because he received assurances from the nominee that he now sees the 2003 invasion of Iraq as a mistake and that he supports winding down the U.S. military mission in Afghanistan.

Democratic defections

Mr. Pompeo’s confirmation by the full Senate got critical support when several red-state Democrats on the ballot this fall, including Sen. Heidi Heitkamp of North Dakota, Joe Manchin III of West Virginia and Joe Donnelly of Indiana, announced this week that they would support him.

In the end, two more Democrats in tough midterm races — Sens. Claire McCaskill of Missouri and Sen. Bill Nelson of Florida — voted to confirm Mr. Pompeo, as did Sen. Angus S. King Jr., a Maine independent who typically votes with the Democrats.

Sen. Doug Jones of Alabama was the only Democrat not running for re-election this year who backed the nomination.

Senate Majority Leader Mitch McConnell, Kentucky Republican, praised Mr. Pompeo while decrying Democratic delaying tactics in a floor speech shortly before Thursday’s vote. He noted that the Tillerson and Pompeo nominations were the first two ever for secretary of state requiring a Senate cloture vote to cut off a filibuster by the minority.

“I guess Senate Democrats are in a history-making mood,” Mr. McConnell said.

Every past nominee to get a roll call vote since at least the Carter administration received 85 or more yes votes in the Senate, and Senate Republicans noted repeatedly in the debate that both of President Obama’s nominees for secretary of state — Hillary Clinton and John F. Kerry — received 94 yes votes.

But Sen. Mark R. Warner of Virginia was one of many Democrats who said Mr. Pompeo’s record as a tea party congressman and military hawk were inappropriate for a secretary of state. Many feared that Mr. Pompeo, unlike Mr. Tillerson, would not serve as a brake on some of the president’s policy moves, notably his harsh criticism of the Iran nuclear deal and his questioning of some of America’s traditional alliances.

“I expect America’s top diplomat to be a forceful advocate for American values around the world — values like freedom, diversity, equality and tolerance,” Mr. Warner said in a statement, “and I was disappointed that Director Pompeo did not take the opportunity offered during the confirmation process to repudiate some of the extreme views he expressed during his time in Congress.”

CIA Deputy Director Gina Haspel, Mr. Trump’s choice to replace Mr. Pompeo as head of the CIA, still faces a tough confirmation battle of her own, primarily over her role in the agency’s tough interrogation practices in the wake of the Sept. 11, 2001, attacks. Her confirmation hearing has been put off until next month.

• This article is based in part on wire service reports.

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