Wimbledon 2019: Stefanos Tsitsipas crashes out of Grand Slam after a thrilling 5-setter
Zverev is one of the leading lights breaking through from the NextGen but he has once again flopped at a Grand Slam.
German Sixth seed Alexander Zverev and seventh seed Stefanos Tsitsipas were surprise casualties at Wimbledon as Jiri Vesely and Thomas Fabbiano progressed.
German Zverev, 22, and Greek Tsitsipas, 20, have both been tipped as future Grand Slam champions but both went out in the space of half an hour.
Czech qualifier and world number 124 Vesely lost the first set but recovered to beat Zverev 4-6 6-3 6-2 7-5.
Italy's Fabbiano then claimed a 6-4 3-6 6-4 6-7 (6-8) 6-3 win over Tsitsipas.
"Overall, I think I played an unbelievable match without many mistakes," said Vesely.
"I was playing really well, serving good and trying to go to the net. The pressure was a little bit on him, but he won the first set and then I started to play. I had nothing to lose anymore.
"After the second set the pressure came back on him. I tried to force it and all of a sudden I was two sets to one up. I think I have done really well today."
He goes on to play either Pablo Cuevas of Uruguay or Bosnia's Damir Dzumhur, while world number 89 Fabbiano will face 40-year-old Ivo Karlovic .
The Croatian, the oldest man to play in the singles event since Ken Rosewall in 1975, beat Italian Andrea Arnaboldi 6-4 6-4 7-6 (7-4).
Anderson and Wawrinka ease through, Lopez continues form
Elsewhere, fourth seed Kevin Anderson won 6-3 6-4 6-2 against Frenchman Pierre-Hugues Herbert, who will partner Andy Murray in the men's doubles later this week.
Anderson only returned to action at Queen's after a three-month lay-off with an elbow injury, but eased past Herbert, who said afterwards he has been managing a thigh injury.
Canadian 19th seed Felix Auger-Aliassime became the first man born in the 2000s to win a Grand Slam main draw singles match with a four-set victory against his compatriot Vasek Pospisil.
In the all-Canadian affair, 18-year-old 19th seed Auger-Aliassime dropped the first set but recovered to win 5-7 6-2 6-4 6-3.
Switzerland's three-time Grand Slam champion Stan Wawrinka also eased through in straight sets, winning 6-3 6-2 6-2 against Belgium's Ruben Bemelmans, while Russian 10th seed Karen Khachanov beat South Korea's Kwon Soon-woo 7-6 (8-6) 6-4 4-6 7-5.
Queen's champion Feliciano Lopez, 37, continued his fine form on the grass with a 6-4 6-3 6-4 win over American Marcos Giron.