The Shrine of Our Lady of Ta' Pinu, with origins shrouded in mystery, first appears in historical records when Bishop Domenico Cubelles noted its reconstruction and ownership by the noble Gentile family. In 1575, Msgr. Pietro Duzina ordered its demolition due to disrepair, but tradition claims a worker's injury during the demolition was a divine sign to preserve it. In 1858, the church was renamed "Ta' Pinu" after Pinu Gauci, who financed its restoration.

The shrine gained fame in 1883 when Karmela Grima reported hearing the Virgin Mary's voice, leading to her miraculous recovery and increased pilgrimages. Bishop Pietru Pace confirmed the heavenly origin of these events, prompting the construction of a new Romanesque church in 1920, completed in 1932 and elevated to Minor Basilica by Pope Pius XI in 1935.

Pope John Paul II visited the shrine in 1990, praying in the chapel and celebrating Mass in its forecourt. In 2010, Pope Benedict XVI honored the shrine by presenting a Golden Rose to the painting of Our Lady. In 2022, Pope Francis also visited Ta' Pinu where he left the gift of a golden rose, which joins the one left by Pope Benedict in 2010 – a traditional gift of popes to Marian shrines. He then presided over a prayer meeting attended by around 3000 representatives of the local Church who had gathered outside the Basilica.

Opposite the church is Ta' Għammar Hill, featuring a series of 14 white Carrara marble statues depicting the Stations of the Cross, starting with the Last Supper and culminating in the crucifixion and burial of Jesus. These statues, sculpted in Italy by Alfred Camilleri Cauchi, were placed along the path in the early 1980s and have become a site of pilgrimage and reflection for many visitors.

The Ta' Pinu National Shrine has been visited by two popes in its history: Pope John Paul II and Pope Francis.