The 38-year-old KTM star started the day over 24 minutes off the pace but finished in second place overall as he came in 4m 03s ahead of Spanish rider Joan Barreda on a Husqvarna.
Despres put himself firmly into the mix for retaining the title as the four-time champion trails teammate Portugal's Ruben Faria by 5m 23s, but admitted it had been about time he made an impression.
"I've got blisters on my feet and my hands are sore, but I had to bang my fist on the table to say: "Hey, I'm here!", said Despres.
While Despres entered the overall picture two of his compatriots fell away completely on the race's longest stage, 852km from Tucuman including 593km of it timed.
David Casteu - who led overnight - hit a cow with his Yamaha which dislocated his shoulder and another stop on the stage saw him slip from pole position to not having a hope of winning the title.
Olivier Pain also had a day to forget as he came off on several occasions and lost about 32 minutes also to lose sight of overall victory.
-AAP