World number one Nadal was in devastating touch against the 15th seed, who struggled throughout and double-faulted on match-point to go down 6-2, 6-4, 6-3 after 2hr 31min on a cool evening at Rod Laver Arena.
Nadal, who caught a virus this month and sweated buckets in Saturday night's encounter with Australian teen Bernard Tomic, said he was now feeling "perfect" just three matches away from a non-calendar year Grand Slam.
"I didn't sweat as much tonight," he smiled. "Two days ago I was sweating like crazy and I felt tired, but today is the first day that I felt perfect physically."
With the win, Nadal moves to 25 consecutive Grand Slam match victories, equalling runs by Jimmy Connors and Pete Sampras in the 1970s and 1990s. Only Rod Laver (29) and Roger Federer (27, twice) have longer streaks.
Nadal will meet David Ferrer on Wednesday in the Australian Open's first all-Spanish quarter-final in 14 years. The French Open, Wimbledon and US Open champion can become the first man to hold all four major titles since 1969.
Earlier Murray barely gave Austria's Jurgen Melzer a look in his 6-3, 6-1, 6-1 win which maintained British hopes of ending a men's Slam drought dating back to Fred Perry's 1936 US Open victory.
The world number five, beaten by Federer in last year's final, said he was surprised by the easy win over the 11th seed which, like Nadal, puts him into the last eight without dropping a set.
"I've played Jurgen in the Slams a few times, including here two years ago, and I was expecting a tough match and I was surprised by beating him in three sets," Murray said.
"I hit the ball well from the start of the match and I played some of my best tennis (here) last year. I don't want to get carried away as I haven't won this kind of thing (major) before." Murray avoided a quarter-final with Soderling when the in-form Swede was on the receiving end of the men's draw's biggest upset, falling in four sets to Ukrainian Alexandr Dolgopolov.
Dolgopolov fought back from a set down to win 1-6, 6-3, 6-1, 4-6, 6-2 in what he called the performance of his life. Two-time Slam finalist Soderling was unbeaten this year and considered a contender for his first major title.
While world number 46 Dolgopolov extends a giant-killing run which also includes the scalp of 2008 finalist Jo-Wilfried Tsonga, Soderling was left to rue an Australian Open jinx which also includes three first-round failures.
"I've struggled many times in this tournament," Soderling said. "And I think, I never had a good first month (of the year) in my career."
Meanwhile Canada's Milos Raonic, 20, was stopped by Ferrer, ending a career-breakthrough streak in which he beat seeds Michael Llodra and Mikhail Youzhny and delivered the tournament's fastest serve.
US Open champion Kim Clijsters remained firm favourite for the women's title after battling past Russia's Ekaterina Makarova 7-6 (7/3), 6-2, setting up a quarter-final date with Pole Agnieszka Radwanska.
"I started the tournament off well (against Dinara Safina) but from then on it has been tough because I have been playing players I've never played before," she said, adding that she was "not Superwoman".
"It was the same tonight. I didn't feel my best out there but I fought back."Women's second seed Zvonareva recovered from a slow start to ease past Iveta Benesova of the Czech Republic 6-4, 6-1 and move towards her third straight Grand Slam final, as she targets a maiden major win.
Zvonareva will next face the Czech Republic's Petra Kvitova, who downed Italian 22nd seed Flavia Pennetta 3-6, 6-3, 6-3.
Polish 12th seed Radwanska saved two match points before defeating Peng Shuai in three sets, leaving Li Na as China's lone hope for a first Grand Slam singles title.