Calvi, the son of a grocer and amateur poet, first sought a literary career but was forced to abandon his studies following what his biographer Grilli Rossi called a "malignant fever" that left him totally deaf (hence his sobriquet "Sordino"). His first artistic training was with the painter Giuseppe Varotti, following which he studied at the Accademia Clementina in Bologna. Although his career was largely spent in and around Bologna, he received commissions throughout Italy (Bergamo, Ascoli Piceno, Bassano and Siena) and abroad (Cracow and Wesel in the Rhineland). The connection with Siena is significant in connection to the present painting which features the two most celebrated Sienese saints, Bernardino and Catherine. Calvi was first recorded in Siena in 1769, the date of a Madonna with Saints Bruno and John the Baptist for the Certosa di Maggiano. He appears there again in 1774, at which time he probably painted the Death of St. Bernardo Tolomei for the Church of Monte Oliveto Maggiore. Other works by him in Siena are in the Church of the Casa di Santa Caterina, in San Pellegrino alla Sapienza, as well as the Pinacoteca Nazionale (a Madonna and Child with St. John, compositionally quite similar to the present work).

The Virgin and Child with Saints Bernardino of Siena, Catherine of Siena, and John the Baptist would seem datable to the period of Calvi's residency in Siena around 1774, not only by virtue of its particularly local subject matter but its stylistic bond to such works as the Martyrdom of St. Bartholomew of 1777 (Church of Santa Maria Maggiore, Bologna) and the Madonna and Child with Saints Girolamo Miani and Thomas Aquinas of 1776 in Bergamo (S. Maria Materdomini), paintings marked by a quiet, elegant classicism.