The 22-year-old fifth seed displayed an impressive combination of brains and brawn to overcome the threat of 6ft 9in Isner and win through 7-6 (7/4), 6-3, 6-2 in a little over two hours.
Murray made just eight unforced errors all match and goes into his first-ever Australian Open last eight clash with a proud record of not having dropped a set in the entire tournament. There, he will meet world No2 Nadal, inset, who came through against 6ft 10in Croatian, Ivo Karlovic 6-4, 4-6, 6-4, 6-4.
But despite being delighted with his own form, Murray is under no illusions as to the task that faces him in the form of the six-time Grand Slam-winning Spaniard.
“It’s been a great start and I was always going to have to play my best tennis. Now the matches are going to get tougher,” he admitted. “I’m happy to have won the matches comfortably. I know the match against Rafa is going to be difficult, but I think I can win, so I just need to make sure I play my best.”
US Open champion Juan Martin del Potro became the highest-profile casualty in the men’s draw after losing 5-7, 6-4, 7-5, 5-7, 6-3 to Marin Cilic.
Fourth seed Del Potro, had no answer to the big-hitting Croat, who fired 71 winners and 20 aces in a three-hour contest. Cilic now takes on Andy Roddick, who came through a four-and-a-half hour marathon with Fernando Gonzalez 6-3, 3-6, 4-6, 7-5, 6-2 under the lights.
Women’s No2 seed Dinara Safina pulled out of her fourth round match with Maria Kirilenko because of a back injury. Safina, who lost to Serena Williams in last year’s final, was serving at 4-5 and 30-40 down when she limped to her chair before conceding.
Russian Kirlenko now takes on Zheng Jie, who became the first-ever Chinese girl to reach the last eight at Melbourne after beating Ukrainian Alona Bondarenko 7-6 (8-6), 6-4.
Former world No1 Justine Henin, playing in her first Grand Slam event since coming out of retirement, is also through to the last eight after a hard-fought 7-6 (7-3), 1-6, 6-3 win over Yanina Wickmayer. She now meets Nadia Petrova after she shocked third-seed Svetlana Kuznetsova 6-3, 3-6, 6-1.