In the lead-up to his confirmation, Pompeo repeatedly said he will seek to "fix" the Iran deal, but he has always left the door open to military action.
The new secretary of state then heads to Israel, Saudi Arabia and Jordan.
Thursday's move to the state department marks the high point so far in the career of the ambitious Pompeo, who some say has his eyes on the White House.
In one notable exchange, Pompeo was harshly grilled by Sen.
But Democrats still openly wonder if Pompeo is qualified to be the top USA diplomat.
The first photos of the meeting between Mike Pompeo and North Korean dictator Kim Jong Un were released Thursday, just hours after Pompeo was confirmed as secretary of state. He replaced Rex Tillerson, who was sacked by President Donald Trump last month.
After graduating from the USA military academy of West Point, Pompeo served as a military officer before obtaining a law degree from Harvard.
The Senate Committee on foreign Affairs approved his candidacy only at the second attempt.
Opponents also anxious that Pompeo was too hawkish, and said his past remarks about homosexuals and Islam made him unsuitable to represent the United States on the world stage. "The administration is moving toward a denuclearized North Korea, and Mike Pompeo has played a critical role in those efforts".
Pompeo will take the helm at the State Department ahead of Trump's expected decision on May 12 about whether to withdraw from the Iran nuclear deal and re-impose sanctions on Tehran.
Other Democrats expressed concern that Pompeo would add to the isolationist tendencies of a president who has indicated he wants to withdraw from the 2015 Iran nuclear accord and who exited a global pact reached that same year that's created to combat climate change. "I do believe in a substantial amount of deference to the president in the choices that he makes to serve him in his administration", Murphy said before giving his reasons for voting against confirmation.
Moments later, the State Department announced his maiden foreign travel. With Pompeo's confirmation imminent, the plane was held on the tarmac until Pompeo could arrive and swap in. Indeed, the timetable for confirmation was moved up a day so that Pompeo could be sworn in immediately and then attend a Friday meeting of North Atlantic Treaty Organisation foreign ministers in Brussels. Pompeo planned to keep up pressure on NATO's European members, particularly Germany, to live up to their past pledges to boost their defense spending. "Now that [Pompeo] has been confirmed by the U.S. Senate, LGBTQ people around the world will need him to stand up for LGBTQ human rights".