Jo Johnson, the younger brother of Prime Minister Boris Johnson, is resigning as an MP and minister, saying he is “torn between family loyalty and the national interest”.
The business minister and Tory MP for Orpington, south-east London, cited an “unsolvable tension” in his role.
Mr Johnson voted Remain in the 2016 EU membership referendum, while his brother co-led the Leave campaign.
BBC political editor Laura Kuenssberg said it was “unbelievable timing”.
Mr Johnson’s resignation follows the removal of the Tory whip from 21 MPs this week for supporting moves to prevent a no-deal Brexit.
Our political editor tweeted that Mr Johnson was “understood to be upset about the purge of colleagues” and that the brothers were “in very different places” on Brexit.
Jo Johnson resigned as a minister last year in protest at Theresa May’s Brexit deal.
But he re-entered government during the summer, after Conservative Party members elected his brother as leader.