As a young man, Panini trained in his native town of Piacenza, under Giuseppe Natali and Andrea Galluzzi, and with stage designer Francesco Galli-Bibiena. In 1711, he moved to Rome, where he studied drawing with Benedetto Luti.
In Rome, Panini earned a name for himself as a decorator of palaces. Some of his works included the Villa Patrizi (1719–1725), the Palazzo de Carolis (1720), and the Seminario Romano (1721–1722). In 1719, Panini was admitted to the Congregazione dei Virtuosi al Pantheon. He taught in Rome at the Accademia di San Luca and the Académie de France, where he is said to have influenced Jean-Honoré Fragonard.