Rex Tillerson, 64, was cleared for full Senate approval in a 56-43 vote.
The vote came after Senate Republicans changed the rules in order to approve President Trump’s nominees for health and treasury, despite a Democratic boycott.
Rex Tillerson, who has never held political office, faced intense scrutiny over his ties to Russia.
The former oil chief forged multibillion-dollar deals with Russia’s state oil company, Rosneft, and was awarded the Order of Friendship by the Kremlin in 2013.
In his Senate confirmation hearing, the Texan native admitted that the West had reason to be alarmed by Russian aggression, but he refused under questioning to label Vladimir Putin a war criminal.
As America’s top diplomat, Rex Tillerson will handle relations with countries including China and Russia and negotiate matters such as climate change and human rights, on behalf of President Trump.
The Senate voted largely along party lines, despite speculation that some Republicans would not approve his nomination.
Though some critics suggested Rex Tillerson would not be able to give up his corporate interests, supporters contended his background as a global dealmaker would bring fresh perspective to the role.
Rex Tillerson’s confirmation was more contentious than those of his predecessors.
The Senate confirmed President Barack Obama’s selections John Kerry 94-3 and Hillary Clinton 94-2.
President George W. Bush’s secretary of state, Condoleezza Rice, was confirmed 85-13 while Colin Powell was approved by a voice vote.
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