By the early 17th century, Spada was active, together with Girolamo Curti, as a member of a team specializing in decorative quadratura painting in Bologna.
[citation needed] His early independent canvases reflect a mannerist style akin to the Flemish Denis Calvaert who resided in Bologna.
His earliest surviving major painting, the altarpiece of the Virgin and Saints Dominic & Francis Interceding with Christ (1604), shows that he had modeled his style on that of Ludovico Carracci.
This is possible since Spada himself painted frescoes in the Magisterial palace of Valletta in 1609-1610; but Caravaggio again had fled to Sicily by 1608, thus their overlap in Malta must have been short.
He painted a large canvas for the Basilica of San Domenico in Bologna, depicting St Dominic Burning the Books of the Heretics, (1616).