In 1500 the Portuguese Fathers (Franciscan Friars) reached Cochin and established the first Portuguese Mission in Cochin, in India. They were followed by the Jesuits (1542), Dominicans (1553), Augustinians (1579), Carmelites (1778), and from 1886 by non religious Portuguese Bishops till 1950. At the arrival of the Portuguese, the Christians in Cochin area joined the Roman Latin Rite.

St. Francis Xavier visited Cochin on several occasions and offered Holy Mass in the St. Francis Church where the famous navigator Vasco da Gama was laid to rest on Christmas day of 1524. A monastery of the Franciscans "Santo Antonio" was established in Cochin in 1518 and two others of the Jesuits in 1550 and 1561. In 1553 the Dominicans founded their College and Monastery in Cochin. The "St. Iago Mission" of Palluruthy was started in 1560 and in 1557 the first printing press in India was established in Cochin.

Because of its singular prominence, Pope Leo X made special mention of Cochin in his Decree erecting the Diocese of Funchal in 1514. In 1534, when the Diocese of Goa was established, Cochin became part of the new diocese.

The Diocese of Cochin was erected on February 4, 1557 by Pope Paul IV in his Decree "Pro Excellenti Praeeminentia". At that time Cochin was the second diocese in India and it exercised jurisdiction over the whole of south, east of India, Burma and Ceylon, The first Bishop of Cochin was a Dominican Friar Dom George Temudo (1557-1567). By the Decree "Pastoralis Officii" of Pope Gregory XIII (13-12-1572) the bishops of Cochin were required to take possession of the Patriarchal See of Goa whenever it became vacant.

In 1663 the Dutch conquered Cochin and destroyed all the Catholic churches and Institutions in Cochin except the Cathedral and the church of St. Francis Assisi. During the British conquest of Cochin, the Cathedral was destroyed. From 1838 until 1886, the Diocese of Cochin was governed by the Vicar Apostolic of Verapoly. After the reorganization in 1886 five Portuguese bishops ruled the diocese.

In 1950 the Portuguese Padroado was suppressed and the diocese was handed over to the native clergy. Dr. Alexander Edezhath (1951- retired in 1975) was the first Indian Bishop. The present Bp John Thattumkal took charge of the diocese on June 25, 2000.

The territory of the Diocese of Cochin is situated between the Arabian Sea in the west, the Archdiocese of Verapoly in the north and in the east, and the Diocese of Alleppey in the south. As per the Executorial Decree issued soon after the Decree of the erection of the dioceses of Cochin and Alleppey, provision is made that the Diocese of Alleppey may have personal jurisdiction of the so called 'Five Hundred Community' who reside within the territory of the Diocese of Cochin and in the same way, the Diocese of Cochin may have jurisdiction over the so called "Seven Hundred Community" in the territory of the Diocese of Alleppey.