In 1959, she was contracted by Rádio Gaúcha and in the next year she travelled to Rio de Janeiro where she recorded her first LP, Viva a Brotolândia.

She won her first festival song contest in 1965 singing Arrastão (The Trawling Net)by Edu Lobo and Vinícius de Moraes, which, when released as a single, made her the biggest selling Brazilian recording artist since Carmen Miranda. The second LP with Jair Rodrigues, Dois na Bossa, set a national sales record and first LP to achieve over one million copies.

Arrastão by Elis also launched her career for a national audience since that festival was broadcast via Tv and radio. As for the history of Brazilian music it represented the beginning of a new music style that would be known as MPB (Músic Popular Brasileira or Brazilian Popular Music), distinguished from the previous bossa nova.

In the late 1960s and early 1970s, Elis Regina helped to popularize the work of the tropicalia movement, recording songs by musicians such as Gilberto Gil. Her 1974 collaboration with Antonio Carlos Jobim, Elis & Tom, is often cited as one of the greatest bossa nova albums of all time, which also includes what many consider the all-time best Brazilian song, "Águas de Março".

She also recorded songs by Milton Nascimento, João Bosco, Aldir Blanc, Chico Buarque, Jorge Ben, Baden Powell, Caetano Veloso and Rita Lee. She possessed an exciting voice and superb intonation, and excelled at up-tempo numbers and ballads under the banner of Brazilian Popular Music Música Popular Brasileira. Her nicknames were "furacão" ("hurricane") and "pimentinha" ("little pepper").

She sometimes criticized the Brazilian dictatorship which had persecuted and exiled many musicians of her generation. In a 1969 interview in Europe, she said that Brazil was being run by "gorillas". Her popularity kept her out of jail, but she was eventually compelled by the authorities to sing the Brazilian national anthem in a stadium show, drawing the ire of many Brazilian Leftists.

She was later forgiven because they understood that, as a mother and daughter, she had to protect her family from the dictatorship at any cost. Along with many other artists Elis was living each verse of Geraldo Vandré's political hymn: Yet they make of a flower their strongest refrain, And believe flowers to defeat guns.

Her rendition of Jobim / Vinicius' song "Por Toda A Minha Vida" appeared on the soundtrack to the 2002 movie Hable Con Ella (Talk to Her) directed by Pedro Almodóvar and her song "Roda" appeared on the soundtrack to the 2005 movie Be Cool.

When Elis Regina died at the age of 36 in 1982, reportedly of an overdose of alcohol and cocaine,, she had recorded dozens of top-selling records in her career. Her death swept the country in mourning. Elis Regina has sold over 80 million albums.

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