In the 1510s he painted frescoes in the Oratory of Santa Maria Nuova in Pilastrello, a Lamentation of the dead Christ in Santa Maria della Passione, a Madonna della Buonanotte in the Abbey of Chiaravalle, frescoes in San Giorgio di Palazzo (1516) and in the Certosa di Pavia, and others.
From 1509 to 1514 Luini completed the frescoes for the Villa Pelucca in Sesto San Giovanni (now in the Pinacoteca di Brera, Milan).
In 1523, Luini painted a polyptych depicting the Enthroned Madonna and Child surrounded by Angels with Musical Instruments, and surmounted by God the Father, found in the Basilica of San Magno, Legnano.
In 1529, Luini completed one of his masterworks, the grand Passion and Crucifixion fresco at Santa Maria degli Angeli [it] in Lugano, paired with other works in the same church.
Later in his career, Luini was increasingly influenced by Leonardo da Vinci, as shown by the St. Anne in the Pinacoteca Ambrosiana and the St. Catherine in the Hermitage.