Ivo Karlovic, the 2016 winner, was unable to get through his opener at the Hall of Fame Tennis Championships.
Nick Kyrgios outlasted fifth seed John Millman 6-4 6-7 (1-7) 7-6 (7-3) in the opening round of the ATP 250 tournament on Monday.
Andy Murray served up a classic in Melbourne as he nears the end of his career, but Roberto Bautista Agut failed to read the script.
Six-time Australian Open champion Roger Federer eased into the second round with a 6-3 6-4 6-4 victory over Denis Istomin.
In the Australian Open's first round, defending champion Roger Federer will face Denis Istomin, while Novak Djokovic will meet a qualifier
Slovakian Martin Klizan won his sixth ATP Tour title with a straight-sets victory over fellow qualifier Denis Istomin at the Generali Open.
Denis Istomin will take on Martin Klizan in the Generali Open final after they overcame Nicolas Jarry and Jaume Munar respectively.
Defending Australian Open champion Novak Djokovic was outdone by Denis Istomin in the second round in Melbourne.
World number two Novak Djokovic felt there was not much more he could have done to avoid a stunning defeat to Denis Istomin in Melbourne.
Denis Istomin caused a huge upset at the Australian Open, shocking two-time defending champion Novak Djokovic in the second round.