Zverev's brother Mischa Zverev was also eliminated, going out 6-3, 6-1 to David Ferrer in the first round, while Kei Nishikori eased to a 7-5, 6-2 win over Taylor Fritz to secure a place in the third round.
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.
Before the tournament, top seed Djokovic declared the three should be favourites to win the Slams, and Federer agreed when asked after his Evans match.
Australian Nick Kyrgios has hit out at Alexander Zverev after a video appeared to show the German dancing at a crowded club on Sunday despite the world No. 7 pledging last week he would be self-isolating. The video was posted on Instagram by German designer Philipp Plein and later deleted. There was no indication when the video was taken.
Dominic Thiem will watch a treasured home movie of his recent win over Novak Djokovic at the season-ending ATP Tour Finals as he seeks inspiration to take down the defending champion Serb in the Australian Open decider.
Alexander Zverev has proven himself as the best of tennis' new generation of men's players
Dominic Thiem, the only player to beat claycourt giant Rafael Nadal on the red dirt this season, is one of the dark horses at the French Open - and the Austrian feels he deserves the tag.
Dominic Thiem fell in straight sets to Rafael Nadal in the 2018 French Open final but took the 12-time Roland Garros champion to four sets last June. On Sunday, the Austrian appeared to be heading towards a four-set victory before Djokovic mounted a spectacular comeback to deny him again.
But for the first time, that golden trio will be having an anxious glance over their shoulders. The past week in London has revealed a new fearlessness in the generation of 20 somethings expected to fill the void when they call it a day.
Top seed and defending champion Roger Federer returned to form to beat Japan's Kei Nishikori 6-4, 7-6(4) and reach the Shanghai Masters semi-finals on Friday.
IMAGES from Day 5 of the 2020 US Open in New York on Friday.
5 exceptional players who surprised us at Melbourne.