Defeat was a blow for the 21-year-old Spaniard as the French Open and Wimbledon champion's bid to become the youngest man to complete a career Grand Slam went up in flames, and he was left to digest his third loss to Djokovic on the surface.
Sweltering heat gripped the second-round action at the US Open on Wednesday
The Russian ended Djokovic's hopes of completing a sweep of all four Grand Slam titles in 2021 when he defeated the Serb in the US Open final in September to pick up his maiden major.
Alcaraz topped the Red Group and will face Green Group runner-up Novak Djokovic in a mouth-watering semi-final.
Germany's Alexander Zverev won the battle of the young guns against Denis Shapovalov on Saturday to set up a Madrid Open final against Austria's Dominic Thiem.
Images from Day 3 of the French Open matches played at Roland Garros in Paris on Tuesday
Carlos Alcaraz suffered a shock 6-1, 7-5 defeat against Norway's Casper Ruud in his opening match at the ATP Finals
Mischa still finds time to tease 'Sascha', despite his little brother's rapid ascent up the tennis rankings.
Alcaraz stops Zverev to set up semi-final of US Open champions
'If someone told me (I would end the year as number one) at that time it was looking quite improbable'
Novak Djokovic was unexpectedly beaten by fifth-ranked Alexander Zverev, quashing his hopes of winning an Olympic singles gold medal, the only major honour missing from his long list of accolades.
World No 1 Carlos Alcaraz fended off in-form American Tommy Paul to reach the Cincinnati Open quarter-finals on Thursday
Zverev has not lost to Wawrinka in two previous meetings but is not taking the 2014 Melbourne Park champion lightly.
In the ongoing Monte Carlo Masters, Jannik Sinner clinched a hard-fought win as Casper Ruud crashed out.
'I don't want to close 100% the door, because it's a very simple thing...'
Zverev's serve played a big role in the victory, his third of the year, as the World No 3 won all but two of his first-serve points in the final, which lasted 74 minutes.
Italy sealed a place in the semi-finals of the ATP Cup by winning both singles matches against France
Images from Day 1 of the French Open matches played at Roland Garros on Sunday
Defending champion Naomi Osaka of Japan was upset 7-5, 6-4 by Belinda Bencic in the fourth round at the US Open on Monday as the Swiss reached the quarter-finals for the second time.
Top seed Alexander Zverev crashed out in the second round of the Stuttgart Open, losing to world number 170 Dustin Brown.
Also in action on the first day at Roland Garros is men's second seed Alexander Zverev who meets Ricardas Berankis of Lithuania on Court Suzanne-Lenglen.
Rafael Nadal trailed in the second set before overcoming No. 5 seed Cameron Norrie of Great Britain.
IMAGES from matches played at the Miami Masters in Key Biscayne, Florida
Penpix of the top men's contenders at the 2021 French Open which begins on Sunday:
Carlos Alcaraz beat Novak Djokovic in the Wimbledon final to win his fourth Grand Slam title.
World number one Novak Djokovic had enough on his plate already on Wednesday without marauding Russian Daniil Medvedev pummelling him to a shock 6-3, 6-3 defeat at the ATP Finals.
Novak Djokovic's bid for a record 25th Grand Slam title kicked off on Monday with an easy win over qualifier Radu Albot in the US Open first round.
Djokovic was soundly beaten by Zverev in the 2018 final, a match played out in an electrifying atmosphere in front of 18,000 fans. This time the arena was empty because of the COVID-19 lockdown, a surreal backdrop for a match with so much riding on it for both men.
With Nadal and Federer both skipping the tournament, Djokovic's sensational exit on Sunday after hitting a line judge in the throat with a ball opened up the field for a younger cohort of players.
Images from Day 8 of the 2021 French Open at Roland Garros in Paris on Sunday
Novak Djokovic marked his return to Serbia, after being stranded in the Spanish resort of Marbella for two months due to the coronavirus lockdown, by announcing that he has organised an event which will be contested across the Balkans. When the world number one had travelled to Marbella with his family in mid-March to visit his younger brother Marko, he had no idea it would be another two months before he could return to his homeland on Sunday.
Roger Federer handed Nick Kyrgios a 6-4 6-1 7-5 tennis masterclass by storming into the fourth round of the U.S. Open on Saturday with a ruthless display that left the Australian talking to himself and waving the white flag.
IMAGES from matches on Day 8 at the French Open
IMAGES from Day 8 of the French Open, at Roland Garros, on Sunday.
Rafael Nadal last appeared in a semi-final at Wimbledon in 2022.
Jannik Sinner overpowered American Taylor Fritz in the final to become the first Italian man to win the US Open singles title.
IMAGES from the Miami Masters played in Key Biscayne, Florida on Tuesday
Canada's Bianca Andreescu upset Greek seventh seed Maria Sakkari to reach the last 32, while Japan's Taro Daniel crushed world number 15 Alexander Zverev.
Sinner won in Cincinnati this week to claim his fifth title of a breakout season before the revelation that he avoided a ban over two positive tests
