Portuondo was born one of three sisters; her mother came from a wealthy Spanish family, and had created a scandal by running off with and marrying a black professional baseball player. Omara joined the dance group of the Cabaret Tropicana in 1950, following her elder sister, Haydee. She also danced in the Mulatas de Fuego in the theatre Radiocentro, and in other dance groups. The two sisters also used to sing for family and friends, and in 1947 joined the Loquibambia Swing, a group formed by the blind pianist Frank Emilio Flynn.
From 1952–1953 she sang for the Orquesta Anacaona, and later in 1953 both sisters joined (together with Elena Burke and Moraima Secada) the singing group Cuarteto d’Aida, formed and directed by pianist Aida Diestro. The group had considerable success, touring the United States, performing with Nat King Cole at the Tropicana, and recording an album for RCA Victor. In 1957 the sisters recorded an album with the quartet. In 1959 Portuondo recorded a solo album, Magia Negra, involving both jazz and Cuban music. Haydee left the Cuarteto d’Aida in 1961 in order to live in the U.S.A. and Omara continued singing with the quartet until 1967.