On April 29, 1955 the Holy Father Pius XII by the Bull “Multorum Fidelium” extended the territory of the Diocese of Changanacherry beyond the river Pamba in Kerala up to Kanyakumari, the southernmost boundary of India. From that day the Bishop of Changanacherry sent priests to be pastors of the Syro-Malabar faithful who have settled in different parts of the extended area. Among the parishes and mission stations instituted by these priests, there were the five Catholic communities of Arukani, Pathukani, Netta, Penu and Anamukham in the district of Kanyakumari. The faithful of these communities were mainly Syro-Malabar Catholics who had migrated from Central Kerala. From 1960 onwards, priests from the Archdiocese of Changanacherry started mission work in the area of the Kanyakumari District. As a result of this missionary work people by and large got converted to Catholic faith. The missionaries trained them in Syro-Malabar Liturgy and spirituality and these activities gradually developed into establishment of parishes and mission stations mainly in the Vilavancode and Kalkulam Taluks in Kanyakumari District. From 1967 onwards, the priests from the Congregation of Mary Immaculate (C.M.I.) also joined the Syro-Malabar mission work in Kanyakumari District. Religious Sisters came forward together with the Diocesan and C.M.I priests to start convents and auxiliary mission services. Their service dates back to 1965 when a convent of the Sacred Heart Sisters was founded at Manjalummoodu, which was later, shifted to Mukkoottukal. The Bishops who have contributed to the mission work in Kanyakumari District up to the formation of the diocese are Archbishop Mar Mathew Kavukatt, Archbishop Mar Antony Padiyara and Archbishop Mar Joseph Powathil.
The Diocese of Thuckalay was erected by the Papal Bull “Apud Indorum” on November 11, 1996. It was erected separating the area of the Archdiocese of Changanacherry that extended over to the state of Tamilnadu. This Diocese was granted jurisdiction over the whole Kanyakumari District and the Taluk of Shenkottai of Tirunelveli District. The then Vicar General of the Archdiocese of Changanacherry, Very Rev. Fr. George Alencherry was appointed the first bishop of the new Eparchy. The establishment of the Diocese and the appointment of the first Bishop were promulgated on December 18, 1996. Very Rev. Fr. George Alencherry was ordained Bishop on February 2, 1997. Mar George Alencherry was elected as the Major Archbishop of Syro-Malabar Church; as a result, Rev. Fr. Philip Kodianthara was appointed as the eparchial administrator of the Diocese. On August 24, 2012, Rev. Fr. George Rajendran, SDB, was declared as the next Bishop of the Diocese, whose Episcopal Ordination and Installation took place on September 16, 2012 at Sacred Heart Church, Padanthalumoodu.
Appreciating the missionary activities and the charitable endeavours of the Diocese, the Holy See through the Prefect of Oriental Congregations promulgated a Decree on October 9, 2017 extending the territorial jurisdiction of the Diocese to the civil districts of Madurai, Theni, Virudhanagar, Sivagangai, Ramanathapuram, Tirunelveli and Thoothukudi of the state of Tamilnadu.