While Baltsa's voice had its technical flaws, particularly a sometimes hollow middle register, she had a stage presence somewhat reminiscent of Callas, a sense of fire and energy, that for her admirers more than made up for those. While a von Karajan protégé, she did not let him persuade her to sing the overly heavy roles such as Kundry that he offered her, and during the 1970s and 1980s was among the predominant lyric mezzos on the international operatic scene, with the occasional carefully planned foray, as her voice matured, into heavier roles such as Carmen, Dalila, Santuzza, and even Eboli in Verdi's Don Carlo.
As a child she showed musical promise (when she was just eight she tried her hand at composing) and when she was 14, her family moved to Athens to allow her to attend at the Conservatoire. In 1965 she graduated and won the Maria Callas Scholarship, which let her further her studies in Munich. In 1968, she made her opera debut as Cherubino in Le nozze di Figaro in Frankfurt, and in 1970 appeared at the Vienna State Opera as Octavian in Der Rosenkavalier. She made her United States debut in 1971 as Carmen at the Houston Grand Opera. She first performed with von Karajan in 1974, and he gave her many prominent roles in his productions in the coming years, including the famous 1977 Salome (as Herodias) and 1979 Salzburg Don Carlo. (In 1986, their different views of operatic drama led to a parting of the ways, patched up only in 1988, shortly before his death.) In 1976, she made her debut at La Scala as Dorabella, making her Covent Garden and Paris Opera debuts later that same year as Cherubino.
Her assertive Rosina in the recording of Il Barbiere di Siviglia on Philips (411 058-2) is an excellent example of her style.