In 1919, Pickthall began working for the Islamic Information Bureau in London which published the weekly Muslim Outlook. In 1920, he went to India to serve as the editor of the Bombay Chronicle. Pickthall studied the history of the Islamic empire in India, and believed that it was destroyed by a series of British conspiracies. In 1927, Pickthall became the editor of Islamic Culture, a quarterly journal published under the patronage of the Nizam of Hydrabad. Pickthall wrote and presented eight lectures on Islamic civilization after being invited to do so by the committee of "Madras Lectures on Islam" in Madras, India. These were later published under the title "The Cultural Side of Islam" in 1961 by S.M. Ashraf Publishers, Lahore.

Pickthall had a great desire to translate the Qur'an beginning when he converted to Islam. He believed that it was an obligation for all Muslims to know the Qur'an. In 1930, Pickthall published The Meaning of the Glorious Koran with the patronage of the Nizam of Hydrabad, in spite of the fact that he believed that the Qur'an, being the word of God, could never be truly translated.