The 45-year-old, one of the biggest-selling rappers of all time, will play at the London stadium on 14 and 15 July.
Eminem's Revival tour comes after the release of his global chart-topping album by the same name, which went to number one in the UK.
The artist - also known as Marshall Mathers - has not played at a London stadium since Wembley in 2014, and he has not been in the UK since his appearances last year at the Reading and Leeds festivals.
His Reading show featured a politically charged speech against Donald Trump.
He told the crowd: "So Reading. I'm not about to stand up here and use this f****** stage as a platform to get all political and s***, but this motherf***** Donald Trump - I can't stand him."
On Thursday, he gave an interview to Billboard saying that, while he did not support Hillary, "anything would be better than Trump".
"A f****** turd would have been better as a president," he said.
The explicit artist hasn't toured for four years and his new album featured collaborations with the likes of Ed Sheeran and Beyonce.
Tickets for his Twickenham shows will go on sale online at 9am on 2 February.