70-year-old Sessions, who was the Senator from Alabama since 1997, was confirmed as America's powerful law enforcement officer by surviving a near-party-line vote by 52 to 47.
Sessions, President Donald Trump's most controversial cabinet appointees, used his short inaugural speech to vow to end "lawlessness" and combat what he sees as a rise in crime.
Trump called Sessions a "great protector of the people".
The final vote for Sessions came after 30 hours of debate from Democrats and a stunning fight between liberal Senator Elizabeth Warren and Senate Republicans which ended in her being forced to sit down after she was accused of impugning Sessions.
Sessions, considered as one of the most conservative lawmakers, resigned as the Alabama Senator later in the night after being confirmed as the 84th Attorney General.
One of the first task on his plate is the win the legal battle for the Trump Administration to get the stay lifted on executive order temporarily blocking all refugee arrivals and immigration from seven Muslim-majority countries to the US.
In the past, Sessions has positioned himself as an opponent of H-1B visas, as he believes that this work visa, popular among Indian IT professionals, displaces American workers.
"It was a special night," Sessions told reporters after his confirmation. "I appreciate the friendship from my colleagues -- even those who, many of them who didn't feel able to vote for me. They were cordial, and so we continue to have good relations and will continue to do the best I can."
Senator Dianne Feinstein, the Democratic lawmaker from California attacked Sessions and questioned his credentials.
"How will this nominee handle an investigation and prosecution into an unprecedented and major foreign intrusion into the election of the president of the United States? Can he be independent of the White House? I do not believe he can," said Feinstein.
"We are disappointed that the Senate chose to turn a blind eye to Jeff Sessions' long record of hostility to civil rights. We intend to be relentless in holdingthis Justice Department accountable," said Kristen Clarke, president and executive director of the Lawyers' Committee for Civil Rights Under Law.
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