Carlos Alcaraz was dumped out of the Astana Open in the first round on Tuesday, suffering a surprise 7-5 6-3 defeat to David Goffin.
Goffin entered the draw as a lucky loser after squandering two match points to lose his final qualification match against Luca Nardi on Sunday, but he produced a fine display to see off the world number one in one hour and 46 minutes.
The Belgian had to rediscover his composure to take the opener after throwing away a 5-2 lead, but ultimately deserved his straight-sets win over the US Open champion.
Speaking on court after his victory, Goffin said: "I always believe that I have the level to cause some trouble against those guys.
"When you play against the world number one on a big stage, big crowd, the fire inside gives you so much power to play your best tennis because you don't have any choice."
Stefanos Tsitsipas was the only other seed in action in Kazakhstan on Tuesday, and he advanced to the round of 16 by beating home favourite Mikhail Kukushkin 6-3 6-4.
The Tokyo Open also lost its top seed, as Casper Ruud fell to a 6-3 6-3 loss to Jaume Munar, who claimed his first top-10 win since beating Alexander Zverev in 2019.
But the likes of Borna Coric and Nick Kyrgios fared better, claiming straight-sets wins over Thanasi Kokkinakis and Tseng Chun-hsin, respectively.
Wimbledon runner-up Kyrgios only dropped four further points on his serve after being forced to save a break point in his opening service game, racing to a dominant 6-3 6-1 win.
Elsewhere, eighth seed Dan Evans fought back to beat Radu Albot 6-7 (3-7) 6-1 6-4, and Alex de Minaur lost 6-3 6-2 to Kwon Soon-woo.