"Though you inherit enormous challenges in the Middle East and around the world, I do believe we can achieve peace and stability in these very, very troubled times," Trump said at the swearing-in ceremony in the White House's Oval Office.
64-year-old Tillerson, who was confirmed by the Senate in a 56-43 vote, was administered the oath of office by Vice President Mike Pence.
His confirmation as the top US diplomat was welcomed by the White House and the Republican party but opposed by Democratic lawmakers in the Senate, who raked up his ties with Russia and President Vladimir Putin.
"These truths include the fact that nations have a right to protect to their interests, that all people have a right to freely pursue their own destiny, and that all of us are better off when we act in concert and not in conflict. There's rarely been conflict like we have in the world today -- very sad," Trump said.
Among those present at the swearing in were White House counselor Kellyanne Conway, chief strategist Steve Bannon, chief of staff Reince Priebus and Press Secretary, Sean Spicer.
Former President George W Bush, former Vice President Dick Cheney, former secretaries of state James A Baker and Condoleezza Rice, former Secretary of Defense Robert Gates, and former Senator Sam Nunn had endorsed Tillerson's nomination.
In remarks on the Senate floor, Democratic Senator Elizabeth Warren said Tillerson's "extensive and longstanding ties with Russia" meant that the US couldn't trust him to be a strong advocate for their interests.
"There have even been reports that this Administration is considering dropping sanctions against Russia. There is bipartisan opposition to that idea in Congress, which will conduct vigorous oversight of the State Department," he said.
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