"I have resigned from Cabinet and surrendered the Conservative Whip," Rudd tweeted.
"I cannot stand by as good, loyal moderate Conservatives are expelled," she said referring to Johnson's decision to expel 21 MPs from the Conservative party for voting against the government.
Rudd was a moderate member of former prime minister Theresa May's government whose endorsement Johnson coveted during his successful UK leadership challenge.
British lawmakers willing to go to court to enforce Brexit delay - BBC
Rudd said in her resignation letter that she could no longer endorse Johnson's commitment to take Britain out of the EU on October 31 even if the two sides fail to reach a negotiated deal.
The 56-year-old said she felt that Johnson's threat of a messy "no-deal" divorce was a useful negotiating tactic to take with Brussels.
"However, I no longer believe leaving with a deal is the government's main objective," she wrote.
"The government is expending a lot of energy to prepare for 'no deal' but I have not seen the same level of intensity going into our talks with the European Union."
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