Senate Democrats are poised to throw away 20 years of friendship and a bipartisan working relationship with Sen. Jeff Sessions to wreak political vengeance on him this week as they consider his nomination for attorney general.

Highlighting the deep partisan divide and the bad blood between Democratic lawmakers and President-elect Donald Trump, the same senators who have socialized and co-authored reams of legislation with Mr. Sessions are under pressure from liberal interest groups to air accusations that he is a racist, a sexist and a homophobe.

Mr. Sessions, who has held an Alabama seat in the Senate since 1997 and has served as the state’s attorney general and as a U.S. attorney, is expected to win confirmation from his colleagues, including support from several Democrats. But it won’t be pretty.

Heading into two days of confirmation hearings that begin Tuesday before the Senate Judiciary Committee, where he serves as a member, liberal activist groups have gone so far as to label him a “white supremacist,” and his Democratic colleagues have expressed doubt about his ability to enforce the law without prejudice.

Mr. Sessions has weathered protests in Alabama by the NAACP, which joined other racial minority groups in urging senators to oppose the nomination.

“The question is what in his record over 40 years suggests that we can trust him to enforce the nation’s civil rights laws, and the onus is on Sen. Sessions to prove, in light of that record, that he is fit for this position,” said Sherrilyn Ifill, president of the NAACP Legal Defense Fund.

Senate Minority Leader Charles E. Schumer, a New York Democrat who has described Mr. Sessions as a “gym buddy,” raised the specter of “troubling things” in the nominee’s past and promised tough questions.

Most of the opposition stems from accusations that in the 1980s, while serving as U.S. attorney for the Southern District of Alabama, Mr. Sessions inappropriately prosecuted black voter rights activists and made racially insensitive comments and jokes.

Those accusations derailed his nomination to the federal bench in 1986.

He was accused then, as he is now, of calling a black U.S. attorney “boy,” describing the NAACP as “un-American” and joking that he thought the Ku Klux Klan was OK until he found out they smoke marijuana.

The government watchdog group Common Cause came out against the nomination, citing his state opposition to the Voting Rights Act, which he argued was outdated. In 2006, however, Mr. Sessions voted to extend the law another 25 years.

The liberal group Democracy for America sent an email to supporters branding Mr. Sessions a “white supremacist” and calling him “anti-woman” because he once voted against the Violence Against Women Act.

Mr. Sessions isn’t fazed by the assault on him or by the objections from his fellow senators. He expected it as part of the partisan process and as an effort by Democrats to distract from Mr. Trump’s agenda, said a source close to the nominee.

Trump transition team officials also said that they have diligently prepared for the hearings and are confident Mr. Sessions is ready for whatever questions he receives.

Still, Mr. Sessions is getting pushback from Democrats with whom he has worked the closest.

Sen. Richard J. Durbin, the chamber’s No. 2 Democratic leader and a member of the Senate Judiciary Committee, emerged from a meeting last week with Mr. Sessions to tell reporters he was “troubled” and “disappointed” by the answers he received about criminal justice reform, illegal immigration and voter ID laws.

“There were no breakthroughs,” he said.

Despite co-authoring with Mr. Sessions groundbreaking legislation that reduces the disparity in sentencing for possession of crack cocaine and powder cocaine, a legal distinction that contributed to mass incarceration of black Americans, Mr. Durbin said he wanted to more evidence that Mr. Sessions would enforce the law fairly.

Pressed by reporters whether he thought Mr. Sessions was a racist, Mr. Durbin said: “I’m never going to call anybody that.”

Later, he added a caveat.

“Certainly there are elements in his background with race questions, and he said to me several times point-blank that this was not an issue as far as he was concerned [and] he believed everyone deserved fair treatment,” said Mr. Durbin. “I have more questions to ask. I spent an hour. He’ll get plenty of questions on this issue and get to explain his position more before the full committee.”

Sen. Jon Tester, Montana Democrat, voiced similar concerns about Mr. Sessions after they met privately on Capitol Hill.

Sen. Sherrod Brown, an Ohio Democrat who co-sponsored 13 bills with Mr. Sessions, announced that he would oppose the nomination.

“I have serious concerns that Sen. Sessions’ record on civil rights is at direct odds with the task of promoting justice and equality for all, and I cannot support his nomination,” he said in a statement.

Elizabeth Taylor, who for nine years served as the Senate Judiciary Committee’s Republican’s chief nominations counsel, said she was confident that the tough questions wouldn’t sink Mr. Sessions.

“I think in the end, the people who worked with him would have that basis of personal knowledge to know that that is a false accusation,” she said about charges of prejudice and racism.

However, she said outside groups that are raising fierce objections to Mr. Sessions could cost him some support.

“Obviously, the members are elected members of Congress,” Ms. Taylor said. “If they feel that their constituents are demanding that they do something, then they are going to listen. These groups represent a lot of constituents.”

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