Djokovic moved on in just under three hours by smacking 15 aces among his 55 winners and he broke Hewitt eight times, compared to four breaks for the 30- year-old Aussie loser.
The 24-year-old Djokovic is now 5-1 lifetime against Hewitt. The Serb also topped the Aussie in the fourth round here in 2008 and is 3-1 all-time against Hewitt in Grand Slam action.
Hewitt is a two-time major champion and was the 2005 Aussie Open runner-up to retired Russian Marat Safin.
The reigning Aussie Open, Wimbledon and U.S. Open titlist Djokovic has now won 36 of his last 38 Grand Slam matches and is seeking a third straight major title and a third Aussie crown. A title this week would put Djokovic in select company, as only four players -- Rod Laver, Pete Sampras, Roger Federer and Rafael Nadal -- have captured three straight Grand Slam championships in the Open era (since 1968).
Djokovic's quarterfinal opponent on Wednesday will be fifth-seeded Spanish star David Ferrer. The powerful Serb is 6-5 lifetime against Ferrer.
The world No. 4 Murray, meanwhile, improved to 16-2 in Melbourne over the last three years with a comprehensive 6-1, 6-1, 1-0 victory over injured Mikhail Kukushkin, as the overmatched Kazakhstani retired from the match with a hip injury.
"It wasn't until I went up 3-0 (that) pretty quickly I realized, you know, he wasn't really moving," Murray said of Kukushkin.
"It's obviously good for me, I get to conserve some energy. Tough for him, first time in the fourth-round of a Slam," Murray added.
Murray, who titled in Brisbane three weeks ago, lost to Djokovic in last year's Aussie finale and was the runner-up to Federer here two years ago.
Up next for Murray will be 24th-seeded Kei Nishikori, who posted a big Day-8 upset by ousting sixth-seeded Jo-Wilfried Tsonga 2-6, 6-2, 6-1, 3-6, 6-3 to become the first Japanese man to reach the quarterfinals at a Grand Slam event since Shuzo Matsuoka in 1995 (Wimbledon).
Nishikori is also the first Japanese man in 80 years to advance to the Aussie Open quarters, since Ryosuki Nunoi and Jiro Satoh turned the trick back in 1932.
"Is feeling unbelievable. My first quarterfinal and beating Tsonga, makes me really happy," Nishikori said. "I hope it's big in Japan. A lot of people messaged me a couple of days ago about the round of 16 and now the quarterfinals. It's really exciting."
Tsonga, who lost to Djokovic in the 2008 Aussie finale, piled up 70 unforced errors, compared to just 30 for the elated Nishikori.
The popular Tsonga was fresh off his season-opening title in Doha three weeks ago.
The men's quarterfinals will get underway Tuesday, as a second-seeded Nadal will take on seventh-seeded Czech Tomas Berdych in a rematch of the 2010 Wimbledon final and a third-seeded Federer will battle 11th-seeded Juan Martin del Potro in a rematch of the 2009 U.S. Open final. Nadal neat Berdych at Wimbledon two years ago, while del Potro stunned Federer in New York in '09.
The former No. 1 Nadal owns 10 major titles, including last year's French Open and the 2009 Aussie Open, as be beat his great rival Federer in the championship match in Melbourne three years ago. The former top-ranked great Federer is the holder of a men's record 16 major titles, including four Aussie Open crowns.