Williams, seeded ninth, had little trouble with Kazakhstan's Galina Voskoboeva, dispatching her 6-2, 6-3 to keep her perfect record on clay courts this year intact at 14-0.
The American star goes on to face Russian Nadia Petrova.
Moving on to the third round was second-seeded Russian Maria Sharapova, who defeated American teenager Christina McHale 7-5, 7-5. The former world No. 1 has already racked up one clay-court title this year, taking last month's Stuttgart event.
Also notching a second-round win was fourth-seeded Petra Kvitova, who got past Russian Anastasia Pavlyuchenkova 7-5, 6-4 at Foro Italico.
Among Tuesday's other winners were American wild card Venus Williams, New Zealand's Marina Erakovic, No. 14 Slovak Dominika Cibulkova, Romanian Sorana Cirstea and Italian Flavia Pennetta.