Williams rolled by Tatiana Poutchek 6-1, 6-2, and earned a second-round pairing against Aravane Rezai in the clay-court tournament.
Top-seeded Maria Sharapova, returning to tournament play for the first time since March, shook off Tsvetana Pironkova, 6-4, 7-6 (7-1). Sharapova received a first-round bye and so will next play in the quarterfinals on Thursday.
While third-seeded Patty Schnyder had little trouble in a 6-1, 6-1 romp past Yung-Jan Chan, the Nos. 6 an 8 seeded players were ousted. Catalina Castano upset sixth-seeded Anna-Lena Groenefeld, 7-6 (7-3), 6-2, and Meghann Shaughnessy stopped No. 8 Sania Mirza, 6-4, 6-3.
Other first-round winners Tuesday were Ekaterina Afinogenova, Anastasija Sevastova, Ekaterina Dzehalevich and Vania King.
The winner of the Istanbul Cup, one of the last tournaments ahead of the French Open, will collect $28,180.
2014: The Year in Music [PHOTOS]