Pompeo, a former Army officer who was a Republican congressman, is regarded as a loyal supporter of U.S. President Donald Trump with hawkish world views.
During his confirmation hearing at the Senate Foreign Affairs Committee, Pompeo rejected those accusations.
Trump sent Pompeo to North Korea three weeks ago to meet the isolated country's leader, Kim Jong Un, ahead of a summit with the US president aimed at convincing Pyongyang to abandon its nuclear weapons program.
Newly sworn-in US Secretary of State, Mike Pompeo, will head from this week's North Atlantic Treaty Organisation meeting in Brussels directly on to high-level talks in Israel, Saudi Arabia and Jordan, his spokeswoman said.
Supreme Court Justice Samuel Alito administered the oath at 2 p.m. on Thursday, CNN quoted State Department spokeswoman Heather Nauert as saying.
Behind the scenes, he made numerous trips overseas to meet foreign political and security leaders, especially in the Middle East. Trump will decide by May 12 whether to restore USA economic sanctions on Tehran, which would be a severe blow to the 2015 nuclear pact between Iran and six major powers.
"The Secretary will then travel to the Middle East, where he will meet with Saudi, Israeli, and Jordanian leaders to discuss critical regional and bilateral issues", Nauert said.
Senators in the Republican-controlled chamber voted 57-42 in favour of Pompeo, who had faced resistance from Democrats anxious about his reputation for hawkishness and past harsh statements about homosexuality and Islam.
Pompeo on Thursday secured the votes of 57 senators, with 42 voting no and one senator absent.
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He will have to quickly address a wide array of pressing worldwide issues, including long conflicts in Syria and Afghanistan, as well as Russian assertiveness.
Pompeo has also pledged to restore the State department's "swagger" in the wake of Tillerson's disastrous management of the building, and is already focused on filling the many vacancies.
Trump fired his first Secretary of State Rex Tillerson in March. Pompeo, who became one of Trump´s closest advisers during his 15 months at the Central Intelligence Agency, faced stiff opposition from Democrats, who anxious he might be too closely aligned with the president.
Pompeo opposed the Iran nuclear accord while in Congress.
The Post editorial, headlined "Confirm Mike Pompeo", noted that the nominee "was tough on Russian Federation, saying conflicts with it were caused by "Russia's bad behavior"..."
"That's not diplomacy, and that's certainly not working with our European allies", Cardin said.
"President Trump and his anti-LGBTQ cabinet continuously underestimate the resilience of the LGBTQ community who will stand strong in our fight for safety, equality, and acceptance at home and overseas - with or without the support of the U.S. State Department".
Pompeo served 4 terms as a Republican congressman from Kansas before Trump tapped him to head the Central Intelligence Agency a year ago. This week, Senator Rand Paul of Kentucky, the nominee's main Republican antagonist, bowed to pressure from President Trump to drop his objections.
Just after Pompeo's vote, the Senate is expected to vote on Richard Grenell to be the next Ambassador to Germany.