Only six of the 14 Democrats who backed Pompeo to be CIA director last year voted for him to become the nation's top diplomat. Sen. Doug Jones, D-Ala., who joined the Senate earlier this year, also supported his confirmation.
Sen. Mark R. Warner, D-Va., the top Democrat on the Senate Intelligence Committee and one of those who changed his vote on Pompeo since last year, said that he was "disappointed" Pompeo had not tried "to repudiate some of the extreme views he expressed during his time in Congress" - such as criticism of American Muslims and opposition to same-sex marriage.
Warner added that he hoped that as secretary of state, Pompeo would stand up for "American values ... like freedom, diversity, equality and tolerance" - and that "if he does, he can count on my assistance and support."
In a statement, President Donald Trump called Pompeo a patriot whose "immense talent, energy, and intellect" will serve the nation well. "He will always put the interests of America first," Trump said. "He has my trust. He has my support."
Pompeo, who grew close to the president as his CIA chief, takes over at State as the United States faces a host of foreign policy challenges. Near term, a deadline looms for extending the Iran nuclear deal and for Trump's historic denuclearization talks with North Korean leader Kim Jong Un.
He'll have a prominent role also in negotiating the Trump administration's relationship with European allies and addressing Russian aggression. On the latter, Pompeo has advocated more punitive actions than the president has been willing to mete out.
In those and other matters, Pompeo is expected to strike a dramatically different tone with Trump than his predecessor, Rex Tillerson, who had a testy relationship with the president that often left them publicly at odds. Tillerson also clashed with the professional staff of the department, who felt marginalised under his leadership. The 74,000 employees, two-thirds of them working abroad, will be looking for early cues that Pompeo appreciates their expertise and wants to return the State Department to its traditional place at the center of U.S. foreign policy.
He will have his hands full filling crucial jobs. Eight of the nine senior staff positions at State are unfilled, as are 60 ambassadorships and 10 of the 22 assistant secretary positions. The department is the only agency in the Trump administration that still has a hiring freeze in place. Pompeo has vowed to address staffing shortages immediately, and end the freeze. Last week, he also indicated to members of the Senate Foreign Relations Committee that he would be open to more funding than the 30 percent budget cut the White House has proposed for the department, telling senators that even if Tillerson had said he wouldn't know what to do with even one additional dollar in funds, "I'll take the extra dollar."
Some will be looking for a return to daily press briefings, which went on hiatus under Tillerson before returning to a pace of twice weekly. State Department employees follow the briefings religiously for statements of policy to guide them.
But his earliest tests will take place in the first few weeks of his tenure, on the world stage.
Pompeo's confirmation was hustled to Thursday ensure he would be able to attend a Friday conference of NATO foreign ministers in Brussels as the newly confirmed secretary of state.
By May 12, Pompeo will have to advise Trump on whether to extend waivers to sanctions suspended under the 2015 Iran deal, a momentous decision that could lead to the United States reneging on its commitments and effectively withdrawing from the pact.
The new U.S. embassy in Jerusalem is slated to open May 14. The move, unilaterally decided by the administration, was overwhelmingly condemned in the United Nations. It will fall to Pompeo to make plans to build a bigger embassy so all the employees in Tel Aviv can work there.
And Pompeo is expected to take a lead role in the run-up to a planned early June summit between Trump and North Korea's Kim, a meeting that could pave the path for talks leading to Pyongyang abandoning its nuclear weapons. Trump dispatched Pompeo to Pyongyang over Easter, and as secretary it is anticipated he will be intimately involved in the summit and any talks that ensue.
