Inside to the left of the nave is the Baptistry and over head the choir loft from which the best view of the interior is obtained. The plan of the vaulted interior is a perfect Latin cross with transepts, apse and nave. The right and left transepts are treated as chapels. At the north end is the chancel with its high altar. Over the crossing of transept and nave, the lofty dome rises over an octagonal drum supported on the arches and pendentives, while to the left and right are richly appointed transept chapels each containing two altars. Light streaming through the high windows in the clearstory and the four medallion windows in the drum of the dome is refracted from wall to wall in soft bluish tones.

The walls of the interior are richly adorned with frescoes and gilded ornament. The interior decorations of San Xavier, though somewhat faded in color are perhaps richer than those of other missions—the elaborate detail of its gilded altars, the bizarre painted statues, the spindled altar rails and wine glass pulpit, are in keeping with the rich traditions of Spain and Mexico.

The sides of the vaulted nave, adorned with frescoes, a painted dado and cornice, are lined with heavily capped pilasters. Frescoes, painted in bold reds, yellows, blues, and browns and outlined in orange and black, recall at once the work of early Spanish painters, the eastern heritage of early Christian art, and at the same time, the hand of a native race attuned to brilliant color. The large frescoes, The Last Supper and The Holy Ghost Descending Upon The Disciples, to the left and right respectively, are said to be the work of a monk from the college of Queretaro. The dadoes painted in imitation of tiles have almost disappeared. Below the molded brick cornice is a colorful frieze decorated with the cord and hem of the Franciscan vestments and the traditional fringe of bell and pomegranate.

The pilasters flanking the nave are adorned with niched figures of saints. On the left (front and rear) are St. Mathew, St. Bartholomew and St. Philip, on the right St. Simon and St. Thaddeus. These apostolic figures and many others set into the high altar and transept chapels are painted and modeled with charming naivete of form and expression. As Duell has suggested, “They were intended for the Indian, and his first lessons in Christianity were through art.”

The frescoes on the pendentives and on the drum and dome over the crossing are especially decorative in that they are painted on the white ceiling in vignette. Here again are figures of various saints. Those decorating the pendentives represent St. Thomas Aquinas, St. Augustine, St. Jerome and St. Ambrose.

In the Gospel Chapel formed by the left transept are two richly carved and gilded altars. The larger one at the end, somewhat resembling the high altar, is dedicated to the Passion of Our Lord, the other, on the right, to St. Joseph. The frescoes on the left wall of this chapel symbolize The Presentation of Our Lord in the Temple (upper) and Our Lady of the Pillar (lower). Here also is the confessional.

The apse, containing the elaborately encrusted high altar, is framed by a wide and stilted chancel arch. On the piers of the arch (left and right) are figures of St. James, St. John, St. Thomas and St. Ignatius Loyola, founder of the Society of Jesus. On the corners of the piers are hung the figures of angels, life-size, said to be the likenesses of the two daughters of the artist who decorated the interior. The apse is separated from the rest of the church by a low spindled chancel rail. The central gate of the hand-carved railing is flanked by two grotesque carvings of lions on the escutcheon of Castile and Leon. In their paws were candlesticks—long since carried away by vandals.

The high altar is dedicated to St. Francis Xavier. A figure of the saint occupies a central niche above the altar table. Around it are carved cherubs and arabesques. Still higher is a brilliantly painted figure of the Holy Virgin. On each side of this central motif the corners of the octagonal apse are lined with elaborately carved and gilded columns and between them the niched figures of St. Peter and St. Paul. Surmounting the altar is the figure of God the Creator. The domed ceiling of the apse is embellished with a shell—a motif frequently used in the decoration of the church. The side walls of the apse are painted with colorful frescoes: The Adoration of the Wise Men and The Flight Into Egypt (right wall) and the Adoration of the Shepherds and the Annunciation (left wall).

A small door in the right wall of the apse leads into the Sacristy, a high square domical chamber containing the sacred vessels and reliquaries. The delicate floral decorations on the sacristy ceiling are especially notable. On the north wall is the Crucifixion, the largest and best preserved of any of the frescoes in the church. A small door in the east wall gives access to the arched cloisters of the patio.

In the east transept is the Epistle Chapel containing, like the Gospel Chapel on the left, two altars—the large altar at the end, dedicated to the Mother of Sorrows, containing a statue of Mary, clothed in a bridal gown donated by an Indian girl in appreciation of an answered prayer. Imbedded in the wall above is an antique wooden cross which formerly bore a “life-size” statue of the crucifixion, though nothing remains now but one arm. It is thought the statue was carried away by vandals. The altar at the left is dedicated to the Immaculate Conception.