Having become the first Japanese man to reach the quarter-finals since Shuzo Matsuoka in 1995, Nishikori must now overturn a 13-2 career losing record against three-time champion Djokovic. Scot Murray, 32 - who triumphed here past year alongside Martina Hingis - and former singles world No.1 Azarenka moved into the quarter-finals with a 7-6 (8-6), 6-3 win over Matwe Middelkoop and Johanna Larsson.
Seeded 12, Wednesday will Djokovic's 41st appearance in a Grand Slam quarter-final. I've been building in the past couple of weeks.
Anger and cutting a disconsolate figure has been a running theme for Djokovic at Wimbledon this year.
Nishikori had to survive heavy attack on his serve early in the second as Djokovic smelled blood, saving four break points, which included a 0-40 game.
"I'd be home if that was the case", Djokovic said, when asked whether he felt Wimbledon's Gods were against him.
At the start of the second, Djokovic was putting Nishikori under enormous pressure again, but the Japanese held firm on serve in a 10-minute game.
Next up for the Spaniard is a blockbuster last four showdown with Serb Novak Djokovic.
It was a case of down but definitely not out as a Rafael Nadal kept picking himself off a slippery and dusty Centre Court surface to storm into the Wimbledon semi-finals with a pulsating 7-5 6-7 (7) 4-6 6-4 6-4 over Juan Martin del Potro.More news: ‘Fortnite’ Season 5, Week 1 Challenges Guide
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"Maybe he has good chance to win the tournament", said Nishikori, who was beaten in four sets by the Serb in the quarter-finals.
Djokovic went on to take the set but there was to be another twist at the start of the fourth when the world number 28 - also known for his obdurate resistance - broke Djokovic again. "I didn't harm the grass", he said.
"I'm not sure what to say right now", U.S. Open finalist Anderson said.
He added: "I played very well in Queen's (where he finished runner-up) coming into Wimbledon".
Djokovic looked in control in the first set.
"It motivates me to do extremely well here because I don't want to sit here and explain my loss".
"To be honest, I thought it was unnecessary to get a warning".
"Post-match I heard that the organisers were planning to cancel my match if Monfils and Anderson went to a fifth".