Foreign Office minister Baroness Warsi has resigned from the government, saying its policy on the crisis in Gaza is "morally indefensible"
She wrote on her Twitter feed that she was leaving with "deep regret".
Lady Warsi, who was previously chairman of the Conservative Party, became the first female Muslim cabinet minister when David Cameron took office in 2010.
The prime minister said he "regretted" that she had not discussed her decision to quit with him before announcing it.
Labour backed Lady Warsi's comments, but Chancellor George Osborne called her resignation "disappointing and frankly unnecessary".
Lady Warsi grew up in Dewsbury, West Yorkshire, and worked as a solicitor before entering politics. She was demoted from the cabinet to a middle-ranking Foreign Office post in 2012, being made minister for faith and communities at the same time.
She wrote on Twitter on Tuesday: "With deep regret I have this morning written to the Prime Minister & tendered my resignation. I can no longer support Govt policy on #Gaza."
Several backbench Conservative MPs have called on Mr Cameron to take a more robust line with Israel amid concerns its actions in Gaza are "disproportionate".