Della Porta was influenced by and collaborated with Michelangelo, and Giacomo Barozzi da Vignola, his teacher of architecture. After 1563 he carried out Michelangelo's plans for the rebuilding of the Campidoglio or Capitoline Hill's open spaces where he completed the façade and steps of Palazzo Senatorio, and the Cordonata capitolina or the ramped steps up to the Piazza del Campidoglio.
After the death of Vignola in 1573, he continued the construction of Il Gesù, the mother church of the Jesuit order, and in 1584 modified its façade after his own designs.
From 1573 he was in charge of the ongoing construction of St. Peter's Basilica, and later, in collaboration with Domenico Fontana, completed Michelangelo's dome between 1588-1590.
Giacomo della Porta completed a number of Rome's fountains from the 16th century; these included the fountains in the Piazza del Popolo, the Fountain of Neptune, Rome and La Fontana del Moro in the Piazza Navona.