Baltsa was born in Lefkada. She began playing piano at the age of six, before moving to Athens in 1958 to concentrate on singing. She graduated from the Greek National Conservatoire in 1965 and then travelled to Munich to continue studying on a Maria Callas scholarship.
Baltsa made her first appearance in an opera in 1968 as Cherubino in The Marriage of Figaro at Frankfurt Opera, before going on to appear as Octavian in Der Rosenkavalier at the Vienna State Opera in 1970. Under the guidance of Herbert von Karajan, she became a regular at the prestigious Salzburg Festival. She became Kammersängerin of the Vienna State Opera in 1980.
Her best-known performance is that of Carmen by Georges Bizet, which she has sung a number of times with noted tenors such as José Carreras, Neil Shicoff, and others. She has also sung works by Mozart (notably Così fan tutte), Rossini (Il Barbiere di Siviglia, La Cenerentola, Semiramide, L'italiana in Algeri), Mascagni (Cavalleria Rusticana), Saint-Saëns (Samson et Dalila), Verdi (Aida, La forza del destino, Il trovatore, Don Carlos), Bellini (I Capuleti e i Montecchi), Offenbach (Les Contes d'Hoffmann) and Donizetti (Il Campanello, Maria Stuarda).
She starred in the Austrian film Duett in 1992, playing an opera singer.
- Milnes, Rodney (26 September 1984). "Athens Festival - New look for familiar favourites". Financial Times. p. 12.
- Clements, Andrew (20 May 1985). "Review of Samson Et Dalila at Covent Garden". Financial Times. p. 17.