Sargsian had won only three matches on clay this season
Sixth seed Andy Roddick has fallen in the first round of the French Open for the second year running.
The American lost 6-7 6-1 6-2 6-4 to Armenian journeyman Sargis Sargsian.
Roddick had seemed to be coming into form at just the right time after claiming his sixth ATP title on clay at St Polten last week.
But the sixth seed was unable to find anything like that form and crashed out in four sets.
"It's weird going from feeling like you're playing pretty well to not really knowing what you're doing," admitted Roddick.
"I just wasn't finding the court. I wasn't doing what I wanted to do. It just felt like I was not only fighting against Sargis but against my own game today.
"I just started unravelling pretty much in the second set, obviously. It got way out of hand in the third set. Even more out of hand in the fourth.
"Then I kind of got it back to where was some hope, but just kind of blew up," was how the American summed up his performance.
Sargsian, 29, next meets either Romanian qualifier Victor Hanescu or Michael Llordra of France.