Cavendish triumphed in a bunch sprint to the line at the end of the flat 164km route from San Luis to Villa Mercedes to take his first victory for his new team, Omega Pharma-Quick Step.
Sacha Modolo (Bardiani Valvole-CSF Inox), and Alessandro Petacchi (Lampre-Merida) took second and third respectively.
Cavendish, who spent just one year at Team Sky before deciding to join a team better set up to serve his sprint ambitions, takes the orange jersey as the current leader in the general classification.
Seven riders made an early break on the stage, stretching out into an eight minute, 30 second lead after 48km, with the peloton happy to let them go.
But after a couple of hours the main bunch, led by Omega Pharma-Quick Step riders, began to pull them back in, and soon enough a sprint finish became inevitable.
Cannondale tried to set up a train for Peter Sagan, while BMC did the same for Thor Hushovd. But it was Cavendish's team who got things spot on.
"The team did a great job for me today," Cavendish said. "We were the first team to start riding, with Martin Velits at the beginning, we were present at the front the whole day. We got help from other teams too, the sprinter teams, but the guys just rode so strong and stayed with me the whole day. It is so nice to have a team with me that is 100 per cent committed. I'm so, so proud of the guys today."
"All the teams are fresh and motivated, so it was real, real chaos," Cavendish added. "It was hard to stay together."
The seventh edition of the race features 10 WorldTour teams and star names including Alberto Contador, Joaquim Rodriguez, Vincenzo Nibali, Tejay Van Garderen and Jurgen Van den Broeck.
A flat stage on Tuesday is followed by four days suited for the climbers, interrupted by an individual time trial on Thursday.