It was founded by the Grey Nuns of the Sacred Heart who went on to establish D'Youville University. Its current address is on Hertel Avenue in North Buffalo, but was founded on the West Side of Buffalo.
On April 30, 2013, Holy Angels staff announced that 2012-2013 would be the final academic year. An e-mail to parents stated, "The Board of Trustees and the Grey Nuns of the Sacred Heart made this decision after many weeks of discussion, data analysis, and deliberation among themselves and with school leaders."