Wozniacki dispatched Japan's Ayumi Morita 6-2, 6-3 to begin her quest for her first Madrid crown. The Dane was runner-up at the event in 2009.
Also notching victories Sunday were third-seeded Francesca Schiavone of Italy, who registered a 7-5, 7-6 (7-2) decision over China's Peng Shuai, and eighth-seeded Russian Maria Sharapova, who rallied to down Arantxa Rus of the Netherlands 2-6, 6-3, 6-2.
Not so lucky, however, was defending champion Aravane Rezai of France, who was ousted by Swedish qualifier Sofia Arvidsson 6-3, 3-6, 6-4.
German Julia Goerges, fresh off last week's victory in Stuttgart, posted a 6-7 (3-7), 6-1, 6-4 win over 14th-seeded Estonian Kaia Kanepi.