Hewitt looked set to come out on top of yet another epic when he held match point having been two sets down to Andreas Seppi, but the Italian served an ace and ended up winning 7-6 (7/4), 6-3, 5-7, 5-7, 7-5.
Hewitt came into the tournament unbeaten this year after seeing off Roger Federer to win the title in Brisbane, so his early exit is a major blow. The 32-year-old said: “I had to try to keep fighting, find a way. I ended up one point from coming back from two sets down.”
Federer’s partnership with Stefan Edberg got off to a winning start as the Swiss posted a 6-4, 6-4, 6-2 victory over Australian wild card James Duckworth. The Swiss had little sympathy with those complaining about the searing heat, which reached 42.2 degrees Celsius, saying: “If you’ve trained hard enough your entire life, or just the last few weeks, and you believe you can come through it, there’s no reason (you can’t). If you can’t deal with it, you throw in the towel.”
Thirteenth seed John Isner did retire from his match against Martin Klizan with an ankle injury. That section of the draw is now wide open after 21st seed Philipp Kohlschreiber pulled out before the start of play with a hamstring problem. One of those two had been expected to reach the fourth round, where they were seeded to meet world No 4 Andy Murray.
Fifth seed Juan Martin del Potro is fancied by many to have a good fortnight, but he had to fight back from a set down to defeat American Rhyne Williams.
There was a remarkable victory, meanwhile, for 18th seed Gilles Simon, who was on crutches at the weekend after twisting his ankle in a match at Kooyong but came through 16-14 in a fifth set against Daniel Brands.
There were also wins for Jo-Wilfried Tsonga, Gael Monfils, Kei Nishikori, Fernando Verdasco, Milos Raonic, Grigor Dimitrov and Feliciano Lopez.