The Swiss 19th seed inflicted one of the big-serving American's most emphatic defeats, 6-3, 6-4, 6-4 in 2hr 22min on Rod Laver Arena.
Wawrinka will now take on the defending champion Roger Federer, whom he partnered to win the doubles gold medal for Switzerland at the 2008 Beijing Olympics.
Wawrinka hit a phenomenal 67 winners, 24 of them aces and 18 off his brilliant backhand and committed just 19 errors in an impressive performance that left Roddick nonplussed.
"I played an unbelievable match and it was one of my best, for sure," Wawrinka said.
"To beat Roddick in three sets, it's really good for me. I am very happy with my game tonight." Wawrinka said.
"I'm playing good since the beginning of the year. I have a lot of confidence with winning in the first tournament of the year in Chennai."
Wawrinka is the only player in the bottom half of the draw to yet drop a set and is unbeaten in his last nine matches.
While it will be the first all-Swiss quarter-final at a Grand Slam, it would also be the latest stage at a major that two Swiss players have met.
Federer defeated Wawrinka in the round of 16 at last year's French Open at Roland Garros.
"I am playing my best tennis ever, so for sure it's going to be different," Wawrinka said.
"Everybody knows that Roger is the best player ever, and we know that when he's playing his best tennis it's always tough to beat him."
Wawrinka trails his close friend Federer 6-1 in their previous meetings.
Wawrinka broke the strong Roddick serve three times and only conceded three break points on his own serve.
He won a dominant 92 percent of first serves and backed that up with 65 percent of second serves in a powerful, controlled serving performance.
Wawrinka dominated the court position and often had Roddick retreating behind the baseline and minimising his angles to combat the Swiss's powerful groundstrokes.
Roddick's only other straight sets defeat at the Australian Open was two years ago when he was thrashed by Federer in the semi-finals.
Roddick yet again came up short at his 10th Australian Open and leaves Melbourne without improving on his four semi-final appearances.
"I didn't have the ability to run back," Roddick said.
"Conditions were colder, so the (backhand) slice wasn't really working.
"I wasn't able to get the ball to jump much, so a lot of the shots he hit were in his pocket and I was having a hard time getting it out of that zone."