Melbourne: As temperatures soared past 40 Celsius, fourth seed Murray barely broke a sweat against Romanian Davis Cup captain Andrei Pavel who retired with a back injury.
Second-seeded Serena Williams was equally comfortable in her 6-3, 6-2 mauling of China’s Meng Yuan.
Matching her sister, sixth seed Venus barely broke stride as she sauntered past Germany’s Angelique Kerber 6-3, 6-3.
While they cruised, Russian fourth seed Elena Dementieva survived a gruelling test before grinding down Germany’s Kristina Barrois in three sets, while Polish ninth seed Agnieszka Radwanska became the biggest casualty so far.
Australian hope Lleyton Hewitt joined Radwanska on the scrap heap after slumping in five sets to Chilean 13th seed Fernando Gonzalez.
Murray is now undefeated in six matches this season as he goes in search of Britain’s first Grand Slam title since 1936.
The experienced Williams is looking for her 10th major crown and her fourth in Melbourne.
Only a few select women, including Steffi Graf, Martina Navratilova and Chris Evert, have won more major titles than the formidable 27-year-old.
The American powered past Meng in just 75 minutes.
“I think I hit some pretty solid shots, sometimes I even went for some shots just to try something different,” she said, downplaying the effect of the heat.
Venus, who has yet to lift the Melbourne title, was untroubled by Kerber.
Dementieva is widely regarded as a dark horse for the championship after already winning two titles this year.
But the Beijing Olympic gold medallist was pushed to the limit in the 7-6 (7/4), 2-6, 6-1 win, emerging victorious to take her recent unbeaten run to 11 matches.
Other players to progress included 13th seed Victoria Azarenka of Belarus, while China’s unseeded Peng Shuai sent Italian 28th seed Francesca Schiavone packing. Wimbledon semi-finalist Zheng Jie beat France’s Camille Pin.
Amelie Mauresmo, the champion in 2006, showed no signs of the thigh strain that forced her out of the Brisbane International in her 6-4, 6-3 win over Olga Govortsova.
On the men’s side, French sixth seed Giles Simon quiety went about his business to beat unseeded Spaniard Pablo Andujar in straight sets.