Second seed Novak Djokovic extended the hottest winning streak in tennis to 27 matches in the third round of the Australian Open as a cool front brought respite to Melbourne after a four-day heatwave.
Spain's David Ferrer continued carving his way through the men's draw largely unnoticed.
Ferrer's compatriot Tommy Robredo caused the biggest upset of the day by edging ninth seed Richard Gasquet 2-6 7-5 6-4 7-6(6) in an evening thriller disrupted briefly by rain.
Djokovic's last defeat was against Rafa Nadal in the U.S Open final and 49 Istomin never looked like stopping his winning run at 26 matches under the closed roof of the Rod Laver Arena.
Looking to become the first man in the professional era to win four consecutive Australian Opens, second seed Djokovic raced through the first two sets in 70 minutes before the Uzbek suddenly upped his aggression to break the Serbian as he was serving for the match.
Visibly piqued, Djokovic was in no mood to risk the possibility of giving up his first set of the tournament and broke back immediately before overwhelming Istomin with the power of his shots to convert his second match point.
"I feel better on the court as the tournament is progressing," said Djokovic, who will take on his Italian friend Fabio Fognini for a place in the quarter-finals.
"Things got tense towards the end of the match. I didn't want to drop the third set, obviously, so I was very focused to get the job done in straight sets."
Temperatures finally drop
Temperatures are forecast to plummet on Saturday, a huge relief to players and organisers alike after four days of rows over what constitutes dangerous conditions.
Ferrer's attritional style was made for hot conditions and he survived a second set wobble to wear down Frenchman Jeremy Chardy and reach the fourth round at a 15th consecutive grand slam with a 6-2 7-6 (7-5) 6-2 victory.
Ranked and seeded third after Andy Murray missed the back end of last season, Ferrer next faces Florian Mayer with Tomas Berdych or Kevin Anderson waiting in the quarter-finals.
Berdych, by contrast, eased into the fourth round without having dropped a set all week courtesy of a 6-4 6-2 6-2 victory over Bosnian qualifier Damir Dzumhur.
With Nadal, Roger Federer and Murray in the other half of the draw, Berdych knows he will rarely have a better chance to
reach a first semi-final at Melbourne Park.
"You know, it's always about the draw," said the Czech seventh seed. "Really, if I'm going to have it once pretty good, yes, I take it."