Manmohan Ghose was the son of Dhan Ghose and his wife, Swarnalata Basu. His younger brother was Sri Aurobindo (Aravinda) Ghose, the politician and spiritual leader.

Manmohan, a brilliant scholar, was educated at Manchester grammar school (1881–4), St Paul's School in London (1884–7) and won an open scholarship to Christ Church, Oxford which he took up in 1887.

Ghose became close friends with Laurence Binyon at St Paul's, bonding over their love for the Classics and Matthew Arnold. Binyon credited Ghose for introducing him to Indian literature, art and philosophy. Binyon joined Oxford a year after Ghose and they collaborated on the poetry publication, Primavera, published in 1890. In the vacations he and his brothers stayed at 128 Cromwell Road, London, the office of the South Kensington Liberal Club. The Liberal Club's secretary was J. S. Cotton, editor of the Academy, who was born in India and whose publication reviewed Primavera. Ghose later met Oscar Wilde at the Fitzroy Street settlement, who reviewed Primavera in the Pall Mall Gazette, with particular favour towards Ghose. During this time in London, Ghose met many other members of the 'Rhymers' Club' set such as Lionel Johnson and Ernest Dowson, who were both very fond of him. Dowson had wished for Ghose's work to be included in The Book of the Rhymers Club that was published in 1892, but Ghose was unable to contribute as he could not share the cost of the expenses.

In 1893, after his father’s death, Ghose returned to India in mourning and took a series of teaching posts in Patna, Bankipur, and Calcutta. In 1897 he was appointed Assistant Professor at Dacca College and full Professor in 1901. After the death of his wife, Malati Banerjee, in 1918, his health deteriorated and he aged prematurely. For thirty years Ghose had cherished the dream of returning to England. In 1924 he booked a passage for himself and his daughters for a date in March, but he died in Calcutta, on 4 January 1924 after a short illness, three weeks before his retirement from Presidency College.