[1] The theatre played an important role in the development of opera and saw the premieres of several works by Francesco Cavalli, as well as Monteverdi's Il ritorno d'Ulisse in patria and L'incoronazione di Poppea.

[2] The librettist of La delia, Giulio Strozzi, became primarily based at the nearby Teatro Novissimo but returned to SS.

Giovanni e Paolo for the 1642–1643 season, bringing with him the singers Barbara Strozzi and Anna Renzi (who sang Ottavia in the premiere of L'incoronazione di Poppea) and the pioneering set designer Giacomo Torelli.

The theatre was described in 1663 by an observer as having: ...marvellous scene changes, majestic and grand appearances [of performers] ... and a magnificent flying machine; you see, as if commonplace, glorious heavens, deities, seas, royal palaces, woods, forests...[5]Marco Faustini[6] became the theatre's impresario in 1660, and for the next fifteen years the Teatro Santi Giovanni e Paolo and the Teatro di San Salvatore a San Luca (owned by the Vendramin family) were to be the dominant opera houses in Venice, each putting on two new operas every year.

An economic crisis made the Teatro Santi Giovanni e Paolo increasingly difficult to maintain, and it finally closed in 1715.