O'Connor was born in Pickering, Ontario and professed as a member of the Basilian Order at the Congregation of St. Basil in 1860. He became a priest at the same congregation in 1863 by John Joseph Lynch.
O'Connor became a theology professor at St. Michael's College in Toronto and Superior of Assumption College in Windsor, Ontario.
O'Connor left his academic posting and was appointed Bishop of Dicese of London, Ontario in 1890 and finally as Archbishop of Toronto in 1899.
O'Connor's academic background made him a strong supporter of education. Under O'Connor, there was a drive for certification for Separate School teachers and he guaranteed an equal education for all Catholics.
He also served as Titular Archbishop of Laodicea in Syria from 1908 and made Archbishop Emeritus in 1911. Forced to resign due to his poor health (O'Connor suffered from Bright's Disease and diabetes) and died in Toronto in 1911. He is buried in a Basilian plot at Mount Hope Catholic Cemetery in Ontario.
A Catholic High School in Ajax is named for him.