Caterina, together with her twin sister Giovanna, was born in Siena to the dyer Jacopo Benincasa and his wife Lapa di Puccio Piagenti. She was the twenty-fourth of 25 children; Giovanna died shortly after birth.

One day, returning home with her brother Stefano, Caterina saw Christ, dressed as the Pope, above the church of San Domenico. Although still very young, this vision deeply marked her soul and led her to decide to give her life entirely to the Lord and to work for the renewal of the Church. At only six years of age, she made a vow of virginity.

In 1364, Caterina joined the "Mantellate" (a group of Dominican laywomen) and began a life of seclusion within her family home. This was a time of intense mystical prayer, culminating in 1367 in the experience of the Mystical Marriage of Faith with Christ who gives her the wedding ring and urged her "to go" for the glory of God. From that moment, Catherine began an active life, dedicating herself to service, especially to the poor and the sick.

In 1372 Catherine began her political activity as a peacemaker among the various Italian states.
During these years, the General Chapter of the Dominican Order appointed Fr. Raymond of Capua as her confessor and spiritual guide.
In 1375, while in Pisa on a mission of peace between the Italian states and the papacy, Catherine received the stigmata in the church of Santa Cristina.
In 1376 she traveled with several companions to Avignon (France) to meet Pope Gregory XI to negotiate with him his return to Rome and to discuss the reform of the Church.
On 13 September 1376 Gregory XI left Avignon and returned to Rome.

After the death of Pope Gregory Catherine firmly supported Pope Urban VI who calls her to Rome. In November 1378, Caterina moved together with some of her companions near the Dominican Basilica of S. Maria sopra Minerva; there, she dedicated all her energies to the cause of the unity of the Church spending long hours in prayer in St. Peter's Basilica, and sending letters and messengers to different parts of the Christian world in support of the legitimate Pope.

At the beginning of 1380, Catherine’s health deteriorated severely. She was no longer able to eat or drink, yet every day she continued to make her way to St. Peter's Basilica – about a mile from her home – where she spent entire days in prayer. She endured unspeakable physical and moral suffering, but continued to dictate letters and to offer her life for the unity of the Church. She offered her life for the Church and died after much suffering on 29 April 1380 in the presence of many of her followers.

Catherine of Siena was canonized by Pope Pius II.

Catherine of Siena was proclaimed Co-Patroness of Italy by Pope Pius XII.

Catherine of Siena was declared Doctor of the Church by Pope Paul VI.

Catherine of Siena was proclaimed Co-Patroness of Europe by Pope John Paul II.