Founded by the Church Missionary Society of England, in 1817 when no institution existed in what was then the princely state of Travancore to teach English.

CMS College Kottayam was patronised by Col. John Munro, the East India Company Resident, and Dewan of Travancore.

The government of India welcomed the college as "a place of general education hence any demands of the state for officers to fill all the departments of public service would be met".

In 1838, the college moved to a wooded hillock — the present site — commanding views of the distant Western Ghats.

In 1880, Visakham Thirunal, Maharaja of Travancore, observed on a visit to the college: "Long before the state undertook the humanizing task of educating the subjects, the Christian Missionaries had raised the beacon of knowledge in the land".

In 1981, the Synod of the Church of South India transferred the management of the college to the C. S. I. Madhya Kerala Diocese.

All significant decisions relating to the college's governance are made by the Council, which convenes no fewer than four times annually.

Research work leading to the degree of Doctor of Philosophy is conducted in the departments of Botany, Zoology, Mathematics, Physics, Chemistry, English, and Commerce.

In 2009, the CMS English department celebrated the Golden Jubilee of the introduction of a postgraduate programme.