In 1866, after she had taught for several years, Isabella was invited by her brother James Mills Thoburn, a Methodist Episcopal missionary in India, to assist him in his educational and missionary work in India.

She delayed her departure until 1869 when the formation of the Women's Foreign Missionary Society of the Methodist Episcopal Church enabled her to undertake missionary work under denominational affiliation and auspices.

[1] In India, Thoburn's work culminated in the founding of an important woman's college, Isabella Thoburn College in Lucknow (1870), as well as a Methodist High School in Kanpur.

[1] Thoburn returned to the United States for a period to study at Lucy Rider Meyer's Chicago Training School for City, Home, and Foreign Missions in Illinois.

In 1887, Meyer appointed her as the first house mother and superintendent of the school's new Methodist Deaconess Home for training female deacons.