Gamerra was born in Livorno, and worked from 1771 at the Teatro Regio Ducale in Milan – an important centre for opera at the time.
Operas based on his librettos include Sarti's Medonte, re di Epiro and Josef Mysliveček's Il Medonte, Paisiello's Pirro, several operas by Antonio Salieri and Mozart's Lucio Silla (though this libretto was modified by Metastasio).
His librettos are in the grand, orderly tradition of Metastasio, but incorporate progressive elements with enhanced use of chorus, ballet, and elaborate scenery.
In 1793, aided by his reputation as a protégé of Metastasio, he was appointed as court librettist in Vienna, and he took to combining comic and serious features to please Viennese taste.
De Gamerra was politically active, and by his revolutionary attitudes incurred the wrath of Emperor Leopold II, who tried unsuccessfully to block his career.