Located in the town of Tilaco, which sits in a beautiful valley of the same name, this Mission is dedicated to Saint Francis of Assisi and was built between 1754 and 1762 by Juan Crespi. Of all the local missions, Tilaco Mission is considered the best-preserved, with subtler and more complex imagery than the others. Its facade is composed of three horizontal and three vertical partitions, with the Franciscan coat of arms displayed prominently above the main entrance. Other figures on the facade include small angels, ears of corn, and an image of Saint Francis.
Amongst the most distinctive elements of Tilaco Mission are four mermaids with indigenous features. There are also structural differences that set Tilaco Mission apart, as it is the only one constructed on an incline, and its bell tower functions structurally as a buttress for the church and is separated from the nave by the baptistery.