The American musician joins previously-announced headliners Kasabian and Muse at the top of the bill.
Festival organiser Melvin Benn called Eminem’s return “beyond exciting,” adding: “His 2013 headline performance was incredible and I can’t want to have him back.”
He said the line-up, which also features south London rapper Giggs and pop-rock group Haim, was “looking stronger than ever.”
Other performers include Atlanta hip-hip group Migos, indie rockers Blossoms and Everything Everything, Charli XCX, Lethal Bizzle and You Me At Six.
Earlier this year the festivals were criticised by music fans after just one female performer was included in the initial line-up alongside 57 men.
American band Against The Current, fronted by Chrissy Costanza, have now been joined by another 16 acts that feature at least one woman, including the all-female Haim and singer-songwriter Ray BLK.
However the festival is still dominated by men, with 80 of the remaining 97 performers being male solo artists or all-male bands.
Eminem’s last slot at the festival was in 2013 and saw him perform renditions of his most popular tracks including Toy Soldiers and Stan, with singer Dido joining him on stage to perform the latter song.
Reading and Leeds Festival 2017 will run in the respective locations between August 25 and 27.
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