"It is impossible to read Attorney General Sessions' firing as anything other than another blatant attempt by @realDonaldTrump to undermine & end Special Counsel Mueller's investigation", House Minority Leader Nancy Pelosi tweeted following Sessions' resignation.
Trump has been critical of Sessions' performance, particularly regarding his treatment of Special Counsel Robert Mueller's probe into Russian interference in the 2016 presidential election. Now, his chief of staff, Matthew Whitaker, 49, will fill in as Acting Attorney General.
'He will serve our Country well.
"So I could see a scenario where Jeff Sessions is replaced ... and that (new) attorney-general doesn't fire Bob Mueller but he just reduces his budget to so low that his investigations grinds to nearly a halt", Mr Whitaker said in a CNN interview in July 2017. "A permanent replacement will be nominated at a later date", Trump said in a follow up post on Twitter.
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The full implications Sessions' exit may have on Mueller's investigation were not immediately clear.
Shortly before Trump's announcement on Wednesday, he held a press conference in which he was asked if was planning on making any changes to his team.
Mr Sessions became the first casualty of a cabinet shakeup that had been expected from Mr Trump following the midterm elections on Tuesday. In that letter, Sessions explained, "we have restored and upheld the rule of law - a glorious tradition that each of us has a responsibility to safeguard".
Mr Sessions was one of Mr Trump's earliest supporters. He said it would spark a "constitutional crisis" if Trump forced out Sessions as a "prelude" to ending or limiting Mueller's investigation.
Mr Sessions also announced the US President's decision to rescind protections for young adults brought into the country illegally as children.