In 1930, she debuted at the Teatro alla Scala in Milan, and in the next year she sang a successful Juliette, in Gounod's Roméo et Juliette, at the Paris Opera. In the same year, she gained a great success with her debut at the Opéra Comique as Lakmé. She soon became one of the leading lyric coloratura sopranos in Europe, especially in Italy and France. Her repertoire included Lucia di Lammermoor, Amina in La Sonnambula, Elvira in I Puritani, Zerbinetta in Ariadne auf Naxos and Cecilia in Il Guarany, among other roles.
As the favorite singer of Brazilian composer Heitor Villa Lobos, she had an artistic partnership with him that lasted many years and made a number of recordings of his compositions, including a famous recording of the Bachianas Brasileiras No. 5.
Bidu Sayão and her husband Giuseppe Danise purchased an oceanfront property in Lincolnville, Maine. After fifteen years with the Metropolitan Opera, she gave her last performance in 1952, choosing to retire from opera while still at the top of her form. For the next two years she was a guest performer throughout the U.S., but in 1957 she decided to retire completely from public performance; two years after that she made her final recording as the soprano soloist on Heitor Villa Lobos' world premiere stereo recording of his cantata Forest of the Amazon with the composer conducting the Symphony of the Air.
Following the death of her husband in 1963, Bidu Sayão lived a quiet life at her home in Maine. She returned to visit Brazil a last time in 1995, for a tribute to her during the Carnival in Rio de Janeiro, and died a few years later at the Penobscot Bay Medical Center in Rockport, Maine. Her ashes were scattered across the Bay in front of her home.
Although Brazilians have always been strong patrons of the opera, at the time Bidu Sayão was struggling to launch her career there was little in the way of government assistance for aspiring singers; throughout her life she spoke about this lack of support. Following her last visit to her homeland, the government prepared plans to honor her memory. In 2000 the Bidu Sayão International Vocal Competition was established to promote Brazilian operatic talent through a world-class competition.
Bidu Sayão's portrait hangs in the lobby at the Metropolitan Opera House in New York City.