Nadal ended the four hour and 48 minute thriller with a backhand volley victor past a lunging Del Potro who ended the contest lying flat on his stomach.
Nadal has 17 while Djokovic has stalled on 12 since completing the career Grand Slam at Roland Garros in 2016. It also highlights the calibre of player Anderson is.
Spain's Nadal and Serbia's Djokovic have won 29 Grand Slam titles between them, including five previous victories at SW19.
Nadal advances to his first Wimbledon semifinal since 2011.
"Friday is another important match against an opponent who is one of the most hard ones that you can face".
"I'm sorry for him, of course", said Nadal.
While Nadal's rivalry with Roger Federer may be considered as the most engaging, it is the Spaniard's rivalry with Djokovic which is the most enduring.
Nadal and Djokovic meet for the 52nd time.
"He is one of the more complex players that I ever saw in our sport".
"But is impossible to win always, even for him (Federer)". Nadal was back to needing one game to claim the set. I tried to resist, maintaining focus. "Obviously I've been very pleased with the way I've played so far on the grass court season".
Nadal had not lost a set prior to his first quarterfinal at the All England Club since 2011, but was taken the distance in an epic encounter between two warriors of the game. Sorry to Juan Martin, he's an wonderful opponent and unbelievable player.
"After nearly five hours, I fell down".
Anderson or Isner to reach first SW19 final?Since 2013, Djokovic has generally had the upper hand on Nadal, winning 11 of their 14 meetings.
Anderson is the first South African to make the last-four since Kevin Curren in 1983.
"Anything could have happened, so this is a big achievement for me to get to the semi-finals at Wimbledon".
"I said at the beginning of the tournament, getting through to the quarters was a big goal of mine", he said. "I've put myself in with hopefully a shot to be playing again on Sunday".
"I'm very, very happy to be in this position right now", said the ninth seed, who has never played on Centre Court at Wimbledon. "Keep on going, you can do this".
QUOTE OF THE DAY: "I'm going to say hers because she's moving those feet now, she's walking, maybe a little too fast" - Seven-time champion Williams on whether she or her daughter Olympia has made greater improvements to their footwork in the last 10 months.