As a child, she wanted to be an actress right from the start. But, as her mother loved to sing, music was always around. Her father was not musically gifted, but loved to listen to Dorival Caymmi and Noel Rosa compositions. At 13, her family moved to Salvador, and she began to frequent the "university circles," intellectual groups gathering around art exhibitions and performances. The access to theater plays strengthened her desire to become an actress. At that time, a novice Caetano Veloso had become the musical partner of the play director Álvaro Guimarães. For Guimarães's short movie Moleques de Rua, Veloso composed a soundtrack which should have had, according to him, his sister singing in it. At 16, Bethânia tried to refuse, as she had never sung under such pressure. But Guimarães loved her timbre, and included her in his 1963 staging of Nelson Rodrigues' musical Boca de Ouro, where she performed a cappella. In the same year, they became acquainted with Gilberto Gil and Gal Costa. Next year, Veloso was invited to organize a Brazilian popular music show at the opening of Salvador's Teatro Vila Velha. The show, called Nós, por Exemplo, included Veloso, Maria Bethânia, Gilberto Gil, and Gal Costa (still under her name Maria da Graça). The show was a success and was reenacted two weeks later, with the addition of Tom Zé (still presented as Antônio José). The success was even bigger, and the group (without Zé) soon presented another show, Nova Bossa Velha, Velha Bossa Nova. In that same year, Bethânia acted alone in her musical Mora na Filosofia, directed by Veloso and Gil.

In January 1965, still a school student earning bad grades, she was surprised by the invitation to substitute for Nara Leão, already an established young singer who had had a problem with her vocal cords, in her highly successful show Opinião. Bethânia's opening on February 13, 1965, was very successful, and her dramatic performance of "Carcará" (João do Vale/José Cândido) launched her as an overnight national success, repeated during the São Paulo season. Because of the sucess, Guilherme Araújo, then assistant for Aluísio de Oliveira at the RCA label, invited her, through Veloso, to record for the label. In May of that year, Bethânia recorded her first single, and some months later, her first LP. On September 26, 1965, the Vila Velha gang opened the show Arena Canta Bahia, at São Paulo's Teatro de Arena. In April 1966, Bethânia, invited by Guilherme Araújo, opened her show Recital at the Cangaceiro nightclub, in Rio. It also opened the way for Guilherme Araújo to become the manager of Veloso, Gil, and Costa (receiving 20 percent for 70 of his songs, he would be sued by Gil in 1992). She also performed at the Barroco nightclub (Rio). In the same year, Bethânia performed in the show Pois É, together with Gilberto Gil and Vinícius de Moraes, at the Teatro Opinião. In the following month, October 1966, Bethânia performed "Beira mar" (Caetano/Gil) at the I FIC. In 1967, she recorded with Edu Lobo the Elenco album Edu Lobo e Maria Bethânia. Through 1970, she would also be featured in the shows Yes, Nós Temos Maria Bethânia (Teatro de Bolso, Rio), Comigo Me Desavim (Teatro Miguel Lemos, Rio), Recital Na Boite Blow Up (São Paulo), and Brasileiro Profissão Esperança (Teatro Casa Grande, Rio).

In 1968, she performed on the LP Veloso, Gil e Bethânia (RCA) and the solo LP Recital na Boite Barroco. In 1969 and 1970 respectively, Bethânia released the LPs Maria Bethânia and Maria Bethânia Ao Vivo. In 1971, she recorded for Philips the LP A Tua Presença. In July, backed by the Terra Trio, she opened at Rio's Teatro da Praia her show Rosa Dos Ventos, which yielded a live album under the same name, produced by Roberto Menescal. In 1971, she went to Europe and performed at the MIDEM (Cannes, France), and in Italy. Next year, she appeared, together with Chico Buarque and Nara Leão, in the film Quando o Carvaval Chegar. The movie's soundtrack was released in 1972 by Philips. Bethânia wrote the lyrics for Caetano Veloso's song "Trampolim," released on her album Drama. A European tour through Italy, Germany, Austria, Denmark, and Norway followed. In 1973, she opened her show Drama, Luz da Noite, also recorded as an album under the same title. Commemorating the tenth year of her career, she opened her show A Cena Muda (1974), recorded and released in November 1974. On June 6, 1975, Bethânia performed in a live show together with Chico Buarque, recorded and released as Chico Buarque e Maria Bethânia Gravado ao Vivo no Canecão. In 1976, she recorded Pássaro Proibido. In July, together with Caetano Veloso, Gilberto Gil, and Gal Costa, she toured Brazil with the show Os Doces Bárbaros, which yielded a film of the same name by Jom Tob Azulay and a double album released by Philips in November 1976. On January 13, 1977, her show Pássaro da Manhã opened, released as a studio LP under the same title, which brought her second gold record. In May 1978, Bethânia released, with Veloso, a live show recorded in LP as Maria Bethânia e Caetano Veloso ao Vivo.

In 1978, the LP Álibi was released (certified as a gold record before hitting the streets, making her the first Brazilian female singer to reach one million sold copies), producing a show with the same name in July of the next year. In December 1979, she released the album Mel, which also brought the show Mel in January 1980. The same year came the LP Talismã. In the next year, she opened her show Estranha Forma de Vida and released her album Alteza. In 1982, Bethânia performed in the show Nossos Momentos. In 1983, she took another turn in her career with the album Ciclo, branching out of her popular formula toward a new acoustic direction. In 1984, she performed in her show A Hora da Estrela, with songs especially written by Veloso and Chico Buarque. The album A Beira e o Mar followed. In 1985, the show 20 Anos opened. The next year, Bethânia signed with RCA for the release of Dezembros, which contained unpublished songs by Tom Jobim, Chico Buarque, and Caetano Veloso, and "Canções e Momentos," written especially for her by Milton Nascimento. In 1988, she recorded Maria, with guest stars Jeanne Moreau and Gal Costa, which also was the name of her show which opened in that year. In 1989, the album Memória da Pele was released, and Bethânia presented the show Dadaya -- As Sete Moradas. Her 25th career anniversary was commemorated with the album and show 25 Anos, with participation from Nina Simone, Hermeto Pascoal, Egberto Gismonti, João Gilberto, and others. In 1982, she released the album Olho D'água, which was included in a major soap opera's soundtrack. Her 1993 album As Canções Que Cocê Fez Para Mim, also a show, was the best-selling record of that year (1,500,000 copies sold). For the label EMI/Odeon was recorded the album Âmbar, and also a show which was recorded live and released in 1997 as Imitação da Vida.