Britain's Andy Murray celebrates after victory in his men's singles match against Ricardas Berankis of Lithuania on the sixth day of the Australian Open tennis tournament in Melbourne. AFP Photo
The 36th-ranked Frenchman raced to a two sets to love lead, before Del Potro pulled back to level the match only for Chardy to go on and win 6-3, 6-3, 6-7 (3/7), 3-6, 6-3 on Hisense Arena.
Reigning US Open champion Murray put away his Lithuanian practice partner Ricardas Berankis 6-3, 6-4, 7-5 on Rod Laver Arena.
The British third seed trailed by a break of serve in the second set and appeared agitated at various stages, hitting his racquet onto the court and yelling at his courtside box before claiming victory.
Murray, who became the first British man to win a Grand Slam title since Fred Perry in 76 years with last year's win at the US Open, will next play the winner of an all-French clash between Gilles Simon-Gael Monfils.
Record 17-time major champion Roger Federer was due to take on rising Australian youngster Bernard Tomic in the third round later Saturday.
Chardy was ecstatic to have beaten the former US Open champion and will now face Italian 21st seed Andreas Seppi in an unexpected fourth round matchup on Monday.
Seppi upset Croatian 12th seed Marin Cilic in another five-setter.
"I beat Murray last year in Cincinnati, but here it's something more because it's the Australian Open, third round, I play a top player," Chardy said.
"It's a big win for me. Maybe the best of my career. I'm so happy, I enjoyed it."
Chardy's potent forehand netted him 44 winners along with 20 aces in his an overall total of 78 winners.
Del Potro, who was playing in his first official tournament of the year, has yet to win from two sets down.
"The tournament is over for me now," Del Potro said. "I have to work hard because the season has just started. I believe in my game, myself."
Murray said he was looking to improve after his win over Berankis.
"I've won in straight sets my first three matches. Every player wants to hit the ball well every day if they can. But the reality is it isn't always going to happen," he said.
"I'm aware I'll need to improve. But you also don't necessarily want to be playing your best tennis the first round of a Grand Slam or of any tournament. You want to try and improve as the matches go on.
"I'm through to the fourth round having not having played my best tennis today. Hopefully I'll improve for the next one."
Elsewhere, 2008 runnerup Jo-Wilfried Tsonga had few problems with Slovenia's Blaz Kavcic, winning 6-2, 6-1, 6-4 to set up an encounter with with fellow Frenchman Richard Gasquet.
Kavcic was backing up after his near five-hour five-set epic win over Australian James Duckworth and was largely a spent force against the seventh seeded Tsonga.
Ninth seed Gasquet took 2hr 25min to get past Croatia's Ivan Dodig in four sets while Canadian power server Milos Raonic was facing German Philipp Kohlschreiber in the remaining third round match Saturday.