St. Dominic's was founded by the Dominican Order in 1870 at the invitation of the Most Reverend Dr. Dorrian, Bishop of Down and Connor on the Falls Road in Belfast.

[citation needed] The school has grown significantly over the years with the addition of the St. Margaret's Wing in 1950s, St. Thomas's Building in 1960s, and the erection of St. Ita's and St.Raymond's in the 1970s.

[5] In the 2019 League Table it was ranked joint sixth with 99.4% of its GCSE exam entrants receiving five or more A* to C grades.

[citation needed] Since 2022, St. Dominic's has collaborated with Friends' School, Lisburn in the development of a Shared Education Signature Project.

[7] Students can participate in a wide range of sporting activities including athletics, netball, basketball, gaelic football, camogie, fitness training, rugby, soccer, swimming, volleyball, trampolining, water polo and dance.