Australian duo Jordan Thompson and Thanasi Kokkinakis starred on a day of shocks at Queen's Club that saw the top three seeds crash out in the opening round.
World No.1 and defending champion Andy Murray was stunned by Sydney's Jordan Thompson, ranked 89 places below the Scot, 7-6 (7-4) 6-2.
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His win came hot on the heels of Kokkinakis's career highlight 7-6 (7-5) 7-6 (8-5) victory over sixth-ranked Canadian Milos Raonic and world No.3 Stan Wawrinka's surprise loss to big-serving Spaniard Feliciano Lopez.
Thompson, who lost in the final round of qualifying on Sunday, stepped up to play Murray following the withdrawal of Britain's Aljaz Bedene due to a wrist injury.
Thompson played the match of his life - but was given a helping hand by the erratic Murray, the five-time champion of this tournament.
The Australian sealed victory with an ace down the middle as he became the first player since Roger Federer to hold serve for an entire match against Murray.
"Definitely the biggest win of my career," Thompson said.
"I took each point at a time. I definitely didn't expect to be winning here in straight sets. I just wanted to enjoy myself."
Wawrinka, the runner-up to Rafael Nadal at the French Open, appeared to be struggling with a left knee injury in the second set.
While Wawrinka's exit wasn't too much of a surprise, given Lopez's recent form and liking for grass, the early departure of third-seeded Raonic in the first match on centre court certainly was.
Kokkinakis's win was his first over a top-10 opponent, as he came back from trailing 6-3 in the second-set tiebreaker to win with a backhand winner into the corner.
"It's a big frustration," said Raonic, who failed to convert any of his eight break-point opportunities.
"Obviously it would have been a lot easier scheduling everything if I was to be here and have many more matches ahead of me."
For the 21-year-old Kokkinakis, who has endured a long road back from multiple injuries and revealed he had considered giving the game away at times, the win left him emotional post-match.
"It's everything. It's huge for me," Kokkinakis said. "I've been out for so long."
Kokkinakis returned to action in May and played three events before Queen's, with his ranking as low as No.993 only last week.
French player Julien Benneteau advanced to the last 16 by beating Britain's James Ward 6-2 6-2.
There were also wins for Viktor Troicki, Jeremy Chardy, Sam Querrey, Gilles Muller, fourth-seeded Croatian Marin Cilic and Russia's Daniil Medvedev.