According to tradition, the place where the church was built was chosen by S. Francesco  from Assisi in 1219: in that year he was in Ancona to embark for Egypt; his journey was motivated by a desire to bring a message of peace in a land devastated by the struggle between Christians and Muslims. The name "ad Alto" would then come from the very words of the saint from Assisi, who pronounced them while he was on the docks of the port, indicating the Astagno hill as a place to erect the first Franciscan convent in Ancona.

The Franciscan complex were widened between 1422 and 1425 beacuse of the increased numebr of monks and these works were supervisioned by Holy Gabriele Ferretti. When he died in 1456 his family asked Carlo Crivelli to paint  "the Vision of the Blessed Gabriele Ferretti" which is housed at the National Gallery of London.

For the same church the artist painted another masterpiece "Madonna and Child", which is housed in the picture -gallery Francesco Podesti in Ancona.

Another imporatnt work of art, Titian's  "Apparition of the Virgin", was commissioned by a Dalmatian merchant called Luigi Gozzi who was welcomed by Ancona and who wished to express his gratitude. It's the first work signed by Titian himself.

After the Italian unification the church lost all its land and power. Furniture, sculptures and paintings coming from the church of San Francesco ad Alto were scattered around the town.

Currently, the Franciscan complex is home to the military district.

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