"As we move to a new phase, I don't believe it is right that I should carry on as the British Commissioner as though nothing had happened," said a statement by Hill, who is commissioner for financial services.
"In line with what I discussed with the President of the Commission some weeks ago, I have therefore told him that I shall stand down," he said, referring to EU Commission chief Jean-Claude Juncker.
"Like many people here and in the UK, I am obviously very disappointed about the result of the referendum. I wanted it to end differently... But the British people took a different decision, and that is the way that democracy works," he said.
Hill said he had come to Brussels despite being "sceptical about Europe" but had become convinced that "despite its frustrations, our membership was good for our place in the world and good for our economy."