As in many other religions, missionary activity is seen by Catholics as a self-fulfilling mission, a sacred act to expand the scope of God’s kingdom. The geographical discoveries, along with the progress of the maritime industry in the 15th–16th centuries, opened a great prospect for “spreading the Gospel” to faraway lands, including Cochinchina (Vietnam). Along with missionary activities, Western civilization also followed the missionaries, who introduced it into the indigenous social life, contributing to the creation of the West–East connection, and the world integration of this land. Based on the many sources, such as the memoirs and correspondence of the missionaries themselves in Cochinchina and the works on the Catholic history of some Vietnamese and foreign researchers, especially the latest studies of Vietnamese historians, the article focuses on studying about missionary activities along with the introduction of Western civilization by missionaries in Cochinchina from the 16th century to the 18th century. The resusts show that the activities of the missionaries under the encouragement policy of the Cochinchina government are the basic factors promoting the process of spreading Western civilized values in Vietnam. This is an inevitable result of the spread of Catholicism which is an important role in the cultural exchange between East and West in Cochinchina in the 16th and 17th centuries. The paper contributes to clarifying the history of the development of Catholic doctrine in Vietnam and affirm the merits of Western missionaries as a bridge to bring European scientific and technical knowledge to Cochinchina.