Bianca Andreescu, the 2019 US Open winner, lost in straight sets to Hsieh Su-wei and two-time Wimbledon champion Petra Kvitova went down in three to Sorana Cirstea.
Stan Wawrinka missed three match points in a five-setter against Marton Fucsovics and Venus Williams refused to quit despite rolling her ankle in a 6-1 6-0 defeat to Italian qualifier Sara Errani.
Picture of the day
Shot of the day
Only one contender. Kyrgios in his crazy five-set win over Ugo Humbert.
Comeback of the day
Wimbledon champion and second seed Simona Halep came from 5-2 down in the decider to oust Australian Ajla Tomljanovic.
Feud of the day
It's hardly Kyrgios/Djokovic, but second-round casualty Tomic's response to criticism from John Fiztgerald was priceless.
Giving it all
Women: Bianca Andreescu (8), Petra Kvitova (9).
Men: Stan Wawrinka (17), Ugo Humbert (29).
Who's up next?
The last Britons standing, Cameron Norrie and Heather Watson, are in action on day four. Norrie faces Russia's Roman Safiullin while Watson meets 21st seed Anett Kontaveit. World number one Ashleigh Barty takes on fellow Australian Daria Gavrilova while Rafael Nadal is last up on Rod Laver against qualifier Michael Mmoh.