Initially named as the Hindu Female School, Bethune School was founded by John Elliot Drinkwater Bethune in1849, as the first school for girls in Calcutta. Born in Ealing in England. John was educated at Westminster School, graduated from Trinity College and later qualified for the Bar to secure an administrative position in Parliament. He was sent to India in 1848, as Law Member of the Governor General's Council and while in India, he willingly undertook the presidency of the Council of Education, apart from his normal official duties.

Within a short time, he became deeply moved and disturbed by the distressing condition of the women in the Indian society and sincerely felt that the illiteracy is the main reason and the root of female abuse and oppression in India. He was convinced that Indian women desperately need to be educated for their awareness of their rights and the ability to voice their protest and solve their problems.

With strong conviction, Drinkwater Bethune became determined to spread education among the women and eradicate the prevailing social evils. He personally took the pain of contacting the then elites of the Bengali society and with the encouragement, cooperation and active participation of the great social reformers like Pandit Ishwarchandra Vidyasagar, Pandit Madan Mohan Tarkalankar, Raja Dakshinaranjan Mukherjee, Ramgopal Ghosh and others, he became successful to establish the first school for girls in Calcutta in 1849, built on a piece of land donated by Dakshina Ranjan at Mirzapur. He named it Hindu Female School, which started with just two students, Bhubanmala and Kundamala, daughters of Pandit Madan Mohan Tarkalankar. However, it regularly started working from 7th May 1849, with 21 girls on its roll. Sarada Devi, a daughter of Devendranath Tagore and Sarada Devi, daughter of Swarnakumari Devi and granddaughter of Devendranath Tagore were also two early students of Bethune School.

As Drinkwater Bethune passed away on 12 August 1851, Lord Dalhousie, the then governor general of India, took the responsibility of the school to carry on his mission. Later, the school was shifted to a new building on the West of Cornwallis Square, where its foundation stone was laid on 6 November 1850, by the Honourable Sir John Litter, the then deputy Governor of Bengal. Subsequently, the Government took charge of the Hindu Female School in 1856 and later renamed it as Bethune School.

Accordingly, the Managing Committee of the school was formed, with Pandit Ishwarchandra Vidyasagar as the Secretary. Much later, in the month of August 1878, with the cooperation and help of Durgamohan Das, Dwarka Nath Ganguly and Anandamohan Basu, Banga Maha Vidyalaya, founded by Miss Annette Akroyd, merged with Bethune School. In the same year, the school achieved the distinction, as the first school for girls in Calcutta, of sending up the first woman candidate, Kadambini Ganguly, for the Entrance Examination of the University of Calcutta.

It is interesting to note that, originally Kadambini Ganguly was a student of Banga Maha Vidyalaya and as she cleared the Entrance Examination, necessary arranged for commencing college classes were made for her in Bethune school to enable her to pursue her studies. That was the beginning of the Bethune College, as well as transformation of Bethune School to Bethune Collegiate School.

Nevertheless, in 1881, Kadambini Ganguly was joined by Chandramukhi Basu and both of them graduated in 1883, becoming the first female graduates in India. After that, Kadambini joined Calcutta Medical College as the first Indian lady student and later became one of the two, Anandi Gopal Joshi being the other, Indian women doctors who qualified to practice western medicine.

In remembrance of John Elliot Drinkwater Bethune, the students of the Institution duly celebrate the Bethune Day on 12th August every year to commemorate the death anniversary of the noble soul.