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.
Celebrity Breakups and divorces of 2014 [PHOTOS]