She made her stage debut in Bratislava in 1968 as Rosina in Rossini's Il barbiere di Siviglia, and successfully auditioned at the Vienna State Opera the following year, which became her base.

She received international recognition for roles such as Mozart's Queen of the Night in Die Zauberflöte and Zerbinetta in Ariadne auf Naxos by Richard Strauss.

In 2019, she portrayed Elisabetta in Donizetti's Roberto Devereux, who leaves her throne, concluding a stage career performing leading roles over 51 years.

[4][14][15] After winning a singing competition in Toulouse, she was then engaged as a soloist of the opera ensemble of the J. G. Tajovský Theatre in Banská Bystrica, Slovakia, from 1968 to 1970.

[17] Since communist Czechoslovakia was going through normalisation, during which the borders to non-communist countries were closed, Medvecká surreptitiously arranged for an audition for Gruberová at the Vienna State Opera in the summer of 1969.

[22] In Vienna, she studied with Ruthilde Boesch, whom she described as a wonderful, tough, diligent teacher, the demanding role of Zerbinetta in Ariadne auf Naxos by Richard Strauss.

Robert Jacobson of Opera News, in his review noted: New, and a brilliant addition to the ensemble, was Edita Gruberova as Zerbinetta, The Slovak soprano is everything one could hope for in this soaring, most demanding role, for she acts enchantingly, sings with great skill and musicality and possesses a voice that not only sails easily to the top, but is filled out with sweetness and quality; she had a triumph, predictably, not only in her big aria, but in the touching duet with the Composer in the prologue as well.

[10] Gruberová appeared as a regular guest at the Zürich Opera, as Marie in Donizetti's La fille du régiment in 1984, as Lucia in 1990, and in the title role of Rossini's Semiramide in 1992.

[10] The same year, she withdrew from all her performances at the Zürich Opera, after Alexander Pereira, then intendant, claimed that her dancer daughter's injury, which forced her to quit dancing, was not an occupational accident.

[29] Gruberová appeared as Donna Anna in Mozart's Don Giovanni at La Scala in Milan in 1987 and as Elisabetta in Donizetti's Roberto Devereux in Vienna in 1990.

The latter became one of her signature roles; in a new production in Munich directed by Christof Loy, she made peace with Regietheater in a dramatic portrayal of the Queen, without losing her distinctive coloratura.

She always performed coloratura ornamentation with dramatic expressiveness, with humour as Zerbinetta, and in rapture with a high trill as the dying Antonia in Offenbach's Les contes d'Hoffmann.

[14] Jürgen Kesting, writing for the FAZ, allegorized her convincing portrayal of the aging Elizabeth I who leaves her throne and drew parallels to her retiring.

More than a dozen of her filmed and televised opera appearances have been released on DVD, including Die Zauberflöte, Così fan tutte, Die Entführung aus dem Serail, I puritani, Norma, Manon, Beatrice di Tenda, and Donizetti's Lucrezia Borgia and Linda di Chamounix, and Ariadne auf Naxos.