The big Argentine was feeble in the opening set, winning just one game, but he picked up the pace to claim a 1-6 6-1 6-2 6-4 victory on Court Suzanne Lenglen.
Del Potro, whose career has been plagued by wrist injuries, withdrew from the this month's Rome Masters with a groin injury, sparking fears about his prospects in Paris.
When he lost the first set in 25 minutes it looked ominous for the 29-year-old but there looked nothing wrong with his movement as he powered past the world number 116.
Former U.S. Open champion Del Potro is playing at Roland Garros for only the second time since 2012 and will be a danger in the top half of the draw.
(Reporting by Martyn Herman; Editing by Ken Ferris)
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