In 1873, Miss Eliza Talcott and Miss Julia Dudley, two American missionaries, opened a private school at Hanakuma, Kobe. The two missionaries founded Kobe Home, a Christian institution for the education of young women, at Suwayama(present Yamamoto-dori 4-chome), Kobe, with the help of Viscount Takayoshi Kuki of the Sanda clan, other Japanese supporters and an American missionary group then in Japan. Kobe Home was renamed Kobe Girls' School, which was changed to Kobe College in 1894.

In 1933, the campus was moved from Suwayama to the present location, Okadayama, Nishinomiya. Kobe College has always stood on its Christian foundation in difficult times. As a result of government reform, Kobe College became the first women's college under the new system.

Kobe College has added new facilities and annexes to its beautiful campus. In 2002, an IT Center was added to the Angie Crew Building. In 2014, the former Building No 2 was renovated, and named the Virginia Clarkson Memorial Building.