Nadal breezed past Federer in straight sets in last month's French Open semi-final, but the Spaniard will know he faces a sterner test on grass as he targets a first Wimbledon final since 2011. Federer, who is chasing a 21st Grand Slam title, trails the rivalry 25-14.
That match will take place on Centre Court after top seed Novak Djokovic takes on Roberto Bautista Agut.
Djokovic is looking to defend his title as he aims for a 16th Grand Slam, while Bautista Agut is through to his first major semi-final having dropped just one set en route to the last four.
The duo have met 10 times, with Djokovic winning seven of them, though Bautista Agut has won their two matches in 2019 - in Doha and Miami.
FRIDAY'S ORDER OF PLAY
(play begins at 1300 BST unless stated)
1-Novak Djokovic (Serbia) v 23-Roberto Bautista Agut (Spain)
3-Rafa Nadal (Spain) v 2-Roger Federer (Switzerland)