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Lawmakers greenlighted the senator as the 84th US attorney general on a mostly party line vote of 52 to 47, with one Democrat, Joe Manchin of West Virginia, voting with the Republican majority.
When the tally was announced, many senators broke into extended applause for their colleague.
Trump has harangued Democrats for slow-walking his nominees, blasting their unprecedented obstruction as a "disgrace."
He appeared particularly angered by the delay on Sessions, who as attorney general would wield enormous power regarding the administration of justice, including on the issue of voting rights.
"Congratulations to our new attorney general," Trump tweeted shortly after the vote.
Sessions, widely seen as an inspiration for Trump's anti-immigration policies, is just the 6th of 15 cabinet members to be confirmed, in addition to the cabinet-rank positions of CIA director and US ambassador to the United Nations.
He takes charge of the Justice Department and its 113,000 employees amid a swirling legal debate over Trump's most controversial White House action to date, an executive order temporarily blocking all refugee arrivals and immigration from 7 mainly Muslim countries.
With Trump using Twitter to bully a judge who rolled back the ban, and an appeals court weighing whether to reinstate it, debate over Sessions grew increasingly acrimonious and personal.
On Tuesday night, February 7, it turned ugly. Senate Republican Majority Leader Mitch McConnell sternly rebuked Democrat Elizabeth Warren for reading a letter written by the widow of slain civil rights leader Martin Luther King Jr that criticized Sessions's civil rights record.
"She was warned. She was given an explanation. Nevertheless, she persisted," McConnell said of Warren's violation of the chamber's rules of decorum.
Warren, a potential 2020 presidential candidate, later said: "I will not be silent about a nominee for AG who has made derogatory and racist comments that have no place in our justice system."
In 1986, Coretta Scott King wrote a letter to the chairman of the Senate Judiciary Committee urging senators to reject Sessions's nomination as a federal judge. His appointment ultimately failed.
"Mr Sessions has used the awesome power of his office to chill the free exercise of the vote by black citizens," King wrote.
Senator Sherrod Brown expressed concern about Sessions in light of Trump's recent executive order.
"We need an attorney general who will be an independent voice beholden to the Constitution and the American people, not the president," Brown said.
The genteel Sessions, who like the president is 70, was an early loyal Trump supporter who became a pivotal figure in his campaign and his transition team.
Sessions grew up in Alabama, in the segregated South. He was a US prosecutor from 1981 to 1993, before serving as the state's attorney general. He won a seat in the US Senate in 1996.
His career was almost derailed when the Senate panel rejected him for a federal judgeship amid concerns over past comments he made about blacks, and voter rights.
At his confirmation hearing last month, Sessions endured pinpoint attacks by Democrats on his civil rights record, but he insisted that "this caricature of me from 1986 was not correct."
Shortly after his confirmation he sought to assuage concerns about how he would run the department.
"I fully understand the august responsibilities of that office," he said.
Sessions also recognized the heated US political debate since Trump's election victory and urged Americans to come together.
"Our nation does have room for Republicans and Democrats," he said.
But Senate Democrat Chris Murphy said he was "scared" about changes Sessions could bring.
Sessions's "history of opposing civil rights, anti-gun violence measures and immigration reform makes him uniquely ill-fitted to serve" as attorney general, Murphy said.
"I want a chief law enforcement official that will be a champion of the disenfranchised and dispossessed, not a defender of discrimination and nativism." – Rappler.com