Since the eighth century the area where today the shrine is located was a consecrated place. Initially, there was a little church, maybe just a chapel, dedicated to St Mario. Then the church was dedicated both to St Zeno and St Valentine, and towards the end of the 16th century St Zeno became the only patron of the church.
In 1596, St Zeno's church along with the Oratory of St Micheletto and the surrounding lands were given to the "zoccolanti friars” of St Francis (the Franciscan friars who wore wooden clogs) for the erection of a monastery. The Franciscans provided to rebuild the church as evidenced by some dates (1614 and 1615) carved respectively on the architrave of the portal of the facade and on the door jamb of the sacristy. These dates indicate with sufficient reliability the final stages of the rebuilding of the church. In 1731 the church was further enlarged and raised, as another plaque in the upper part of the facade recalls. After these works the Franciscan friars entitled the church to Saint Francis of Assisi and dedicated themselves to an intense ministry of preaching, of confession, and also of material assistance to the neighbouring populations, arousing the fervour and attracting many faithful.
By being defeated Napoleon and being collapsed the Italic Kingdom, in order to fulfil numerous and nagging petitions raised by the population, which begun to make hear their voices since 1805, and for the determining interest of Don Giuseppe Turri, on 26th June 1816 the Austrian government eventually granted the reopening of the church for worshipping. After many and unfortunately useless attempts to make the Franciscan friars come back, Don Turri turned his attention elsewhere. Having known the Redemptorists in Vienna in 1830 and informed of their intention to open a house in Tyrol, he thought that they could be interested in taking care of this church and living in the house that he had already started to build north-westward. This plan was accomplished in 1856, and on 2nd August 1857 the Redemptorist missionaries officially took possession of the church of St Francis and of the annexed religious house.
The devotion to Mary under the title of Mother of Perpetual Help began in Bussolengo in 1875, when the Redemptorist missionaries brought from Rome an original copy of the authentic icon of our Mother of Perpetual Help. This original copy is the number 207 and has been blessed by Pope Pius IX.
In 1952 the Redemptorists began a radical restructuring of the house under the direction of the architect Ugo Zanchetta. Between 1962 and 1965 a radical transformation took place also in the church, which was expanded with the addition of two side navates and completely renovated inside; this work has been directed by the architect Banterle. The church dedication to St. Francis remains unchanged but it was transformed into a Shrine of Our Mother of Perpetual Help. In 1993 the Redemptorist missionaries did a conservative intervention on the frescoes of the sacristy and of the cloister, as well as on the tuff pillars of the arched porches of the same cloister.
In 2005 the Shrine of Our Mother of Perpetual Help is declared "Marian Diocesan Shrine" by the Bishop of Verona Monsignor Flavio Roberto Carraro.