From the Great Dome to the choir loft, the ceiling is covered by five giant murals. Beginning at the loft, they depict: Mary as Queen of Patriarchs, Queen of the Apostles, Queen of the Angels, Queen of the Prophets, and Queen of the Martyrs. The two walls on the Basilica's sides feature huge paintings depicting the Slaughter of the Innocents, the Flight into Egypt, and, of course, the Birth of Jesus at Bethlehem.

But perhaps the most dramatic work of art appears in the Great Dome. The decoration of the structure, 80 feet in diameter and close to 120 feet from the floor, is a true masterwork. The theme is the Assumption and Coronation of the Blessed Mother. In bright colors on a blue sky-like background, numerous figures share in Mary's triumph. Around the dome's outer edge, the 12 apostles and three archangels are shown, while an angelic host carries Mary heavenward. Slightly higher within the dome, her destination is seen: the Holy Trinity awaits her (Jesus is in red robes). A dove (symbolizing the Holy Spirit) is at the very top of the work.