With a heritage that goes back to more than a hundred years, Cotton College, the premier seat of higher learning in Northeast India, unequivocally occupies the pride of place among the institutions of its kind in the North-Eastern part of the country. Having contributed significantly to the academic and cultural life of the region the institution has not only withstood the test of time but has also carved a niche for itself in the sphere of higher education in the country. Contemporaneous with Murarichand College of Sylhet (now in Bangladesh) of the undivided India under the British rule, Cotton College came into existence on 27th May, 1901 through the untiring efforts of such magnanimous and illustrious sons of the soil like Late Manik Chandra Barooah and Rai Bahadur Bhuban Ram Das, backed by the unstinted support of the intelligentsia of the region of that time. However, had it not been for the unreserved support and concern of the then Chief Commissioner of the then Assam Province from 1896 to 1902, Sir Henry John Stedman Cotton, K.C.S.I., the institution would not have perhaps seen the light of day. While the time came, therefore, to express their sense of gratitude to the foremost popular ruler of the province, the people of 'Gauhati' decided to name the institution itself after him.

The first admission to the college took place on 17th June, 1901 with 37 students in the first year F.A. class and 2 students in the second year of the same course. The faculty was consisted of only five members including Prof Frederick William Südmersen (1871 – 1953), the first Principal of the college from 1901 to 1926. The other four faculty members were Prof. Chunilal De, Prof. Indu Bhusan Brahmachary, Prof. Paresh Nath Lahiri and Prof. Maulvi Abu Nasr Muhammad Oheed. Classes during the initial years of the establishment of the college were held in the building which presently houses Chemistry Department of the college. However, no girl student was admitted to the course. It was only in 1929 that two girl students were admitted to the first year Intermediate (Science) class of the college for the first time thus marking the beginning of co-education in the history of higher learning in this part of the country.

The college was first affiliated to Calcutta University, Kolkata. It was under this university itself that the institution developed into a full-fledged Degree College and barring Persian, secured affiliation for the Honours course too in all the subjects taught then. However, with the establishment of Gauhati University in 1948, it became one of its original constituent colleges. Although Post-Graduate classes in certain subjects like English, Economics and Botany were introduced in the college at different points of time under Calcutta University itself, such classes had to be finally discontinued as part of economy drive and also because of the establishment of Gauhati University.

It was only in 1969 that the Assam State Government decided to introduce PG classes in Physics in the college on a permanent affiliation basis. Subsequently, the benefit of PG classes was extended to other subjects as well and finally on 17th October, 1992 , the then Hon'ble President of India, Late Dr. Shankar Dayal Sharma at a glittering function held in the premises of the college formally declared Cotton College as a Post-Graduate institution. Cotton College has become the Constituent College of Cotton College State University (CCSU) w.e.f. September, 2011 through the Cotton College State University Act, 2011. In 2016, Cotton College was reaccredited (third cycle) Grade ‘A++’ by the National Assessment & Accreditation Council (NAAC) with CGPA 3.76 and the University Grants Commission (UGC) recognized it as a ‘College with Potential for Excellence (CPE)’ in 2005. The CPE status has been revalidated in 2010 and again in 2015. The College is also recognized by UGC as a ‘Special Heritage College’, under the scheme ‘Special Heritage Status to Colleges’ in 2015.    

The present day College has an infrastructure built on a sprawling campus covering an area of about 34 acres in Panbazar locality and about 6.4 acres in Rupnagar locality (second campus) of the city of Guwahati. The facilities include a modern library well stocked with books, journals as well as rare manuscripts and with UGC INFLIBNET-NLIST e-journal browsing facility; well equipped laboratories in different academic departments; a Central Instrumentation Centre; a full fledged Department of Computer Science & IT; a well equipped Centre for Mass Communication & Journalism (named as Dr Bhupen Hazarika Centre for Mass Communication & Journalism), a vibrant Placement Cell, a dynamic Entrepreneurship Development Cell (EDC), a Foreign Language Programme Unit and a state of the art Bioinformatics Infrastructure Facility (BIF) Center. In addition to these facilities, the College also has a hospital, a Career & Counseling Cell, a Peace Station, a Guest House, separate hostels for girls and boys, quarters for faculty and office staff, an Indoor Stadium with a modern gymnasium, a canteen, a coffee house and a State Bank of India ATM. All the Academic Departments, Centers and the College office are connected with round the clock internet connectivity. In the year 2003, an ‘Internal Quality Assurance Cell’ was established to look after the internal quality of the institution for continuous assessment of academic excellence.
A ‘Board of Governors’ constituted by the Government of Assam sits from time to time to decide on the policy matters relating to the academic and administrative activities of the College. Moreover, the Council of the Heads of the Departments and the Staff Council are two empowered decision making bodies of the College.