The big-serving 13th seed, who had been struggling with an ankle problem, gamely played on for 82 minutes before throwing in the towel while trailing 6-2 7-6(6) in his first round contest.
It was not just the players who were struggling with the intense heat in Melbourne as a ballboy on court eight required medical treatment after fainting during Milos Raonic's 7-6(2) 6-1 4-6 6-2 victory over Daniel Gimeno-Traver.
Jo-Wilfried Tsonga fired down 15 aces as he got the better of Italian Filippo Volandri in straight sets.
Tsonga, who lost to Roger Federer at the quarter-final stage last year, overcame Volandri 7-5 6-3 6-3 courtesy of five breaks of serve.
He will now face Thomaz Bellucci, who progressed after Julien Reister retired.
World number five Juan Martin del Potro advanced to the second round with a 6-7 6-3 6-4 6-4 win over American qualifier Rhyne Williams in stifling heat.
The towering Argentine, who won the 2009 US Open, is a dark horse to win his second Grand Slam title having enjoyed encouraging form in the lead-up to Melbourne with victory in the Sydney International warm-up event.
The 22-year-old Williams, ranked 130 in the world, had other ideas as he matched Del Potro's firepower in a tense first set and closed it out when the fifth seed stumbled in an error-strewn tiebreak.
Del Potro steadied in the second set and cruised to victory in just over three hours to set up a clash with Spain's 62nd ranked Roberto Bautista Agut.
"I tried to focus for the match in the worst conditions to play," Del Potro said in a courtside interview. "Really, really hot but the crowd kept me going.
"Hopefully the weather will be better on Thursday."
Del Potro is unlikely to get his wish, however, with the temperatures forecast to exceed 40 degrees Celsius for the next three days until a cool change on the weekend.
Asian number one Kei Nishikori endured a gruelling five-set marathon in the Melbourne heat before taking his place in the second round with a 6-3 5-7 6-2 4-6 6-2 win over Marinko Matosevic.
The 16th seeded Japanese got the better of his Australian opponent after three hours, 40 minutes in the full glare of the sun on court two, sealing the victory when an exhausted Matosevic slapped a backhand into the net.
"Nish! Nish! Nish!" chanted the large Japanese contingent in the crowd, who had more than held their own against the vocal locals, particularly as the tiring players slugged it out in a deuce-heavy final set.
Nishikori, watched by new coach and former French Open champion Michael Chang, next meets Serbian Dusan Lajovic as he bids to match, or even better, his run to the quarter-finals at the "Grand Slam of the Asia-Pacific" in 2012.
Men's number 21 seed Philipp Kohlschreiber withdrew from the tournament with a recurrence of a left hamstring problem before his match against Aljaz Bedene, who was instead defeated 7-6(3) 6-3 6-0 by French lucky loser Stephane Robert.
Three of the "Big Four" of men's tennis also get their campaigns underway on Tuesday with Roger Federer having braved the daytime heat against local wildcard James Duckworth and Andy Murray to come. World number one Rafa Nadal faces Bernard Tomic in the relative cool of the evening.
First round results
1-Rafa Nadal (Spain) beat Bernard Tomic (Australia) 6-4 (Tomic retired)
4-Andy Murray (Britain) beat Go Soeda (Japan) 6-1 6-1 6-3
5-Juan Martin Del Potro (Argentina) beat Rhyne Williams (U.S.) 6-7(1) 6-3 6-4 6-4
6-Roger Federer (Switzerland) beat James Duckworth (Australia) 6-4 6-4 6-2
10-Jo-Wilfried Tsonga (France) beat Filippo Volandri (Italy) 7-5 6-3 6-3
11-Milos Raonic (Canada) beat Daniel Gimeno-Traver (Spain) 7-6(2) 6-1 4-6 6-2
Martin Klizan (Slovakia) beat 13-John Isner (U.S.) 6-2 7-6(6) (Isner retired)
16-Kei Nishikori (Japan) beat Marinko Matosevic (Australia) 6-3 5-7 6-2 4-6 6-2
18-Gilles Simon (France) beat Daniel Brands (Germany) 6-7(4) 6-4 3-6 6-3 16-14
22-Grigor Dimitrov (Bulgaria) beat Bradley Klahn (U.S.) 6-7(7) 6-4 6-4 6-3
24-Andreas Seppi (Italy) beat Lleyton Hewitt (Australia) 7-6(4) 6-3 5-7 5-7 7-5
25-Gael Monfils (France) beat Ryan Harrison (U.S.) 6-4 6-4 6-4
26-Feliciano Lopez (Spain) beat Somdev Devvarman (India) 6-4 6-4 7-6(2)
27-Benoit Paire (France) beat Frank Dancevic (Canada) 7-6(12) 6-3 6-4
31-Fernando Verdasco (Spain) beat Zhang Ze (China) 5-7 6-3 6-2 6-3
Nick Kyrgios (Australia) beat Benjamin Becker (Germany) 6-3 6-7(5) 6-2 7-6(2)
Roberto Bautista (Spain) beat Tim Smyczek (U.S.) 6-2 6-1 6-1
Michael Berrer (Germany) beat Michael Llodra (France) 6-4 7-5 6-1
Thomaz Bellucci (Brazil) beat Julian Reister (Germany) 4-6 6-3 7-6(5) (Reister retired)
Teymuraz Gabashvili (Russia) beat Sergiy Stakhovsky (Ukraine) 6-7(3) 6-4 6-2 6-0
Blaz Kavcic (Slovenia) beat Radek Stepanek (Czech Republic) 6-7(3) 4-6 6-1 2-0 (Stepanek retired)
Blaz Rola (Slovenia) beat Federico Delbonis (Argentina) 6-4 6-2 7-5
Dusan Lajovic (Serbia) beat Lucas Pouille (France) 6-4 7-6(9) 4-6 6-3
Victor Hanescu (Romania) beat Peter Gojowczyk (Germany) 7-6(5) 7-6(5) 6-3
Stephane Robert (France) beat Aljaz Bedene (Slovenia) 7-6(3) 6-3 6-0
Michal Przysiezny (Poland) beat Horacio Zeballos (Argentina) 6-3 7-6(4) 7-5
Lu Yen-Hsun (Taiwan) beat Jimmy Wang (Taiwan) 6-3 6-2 6-1
Marin Cilic (Croatia) beat Marcel Granollers (Spain) 4-6 4-6 6-3 6-3 6-2
Thanasi Kokkinakis (Australia) beat Igor Sijsling (Netherlands) 7-6(4) 0-6 7-6(3) 6-2
Jack Sock (U.S.) beat Tobias Kamke (Germany) 7-6(5) 5-7 6-2 6-4
Vincent Millot (France) beat Wayne Odesnik (U.S.) 7-5 4-6 6-7(4) 6-1 6-3
Donald Young (U.S.) beat Robin Haase (Netherlands) 6-7(4) 7-6(2) 6-2 1-0 (Haase retired)