[1] The ministry is responsible to the Ontario Legislature through the minister of health, presently Sylvia Jones since June 24, 2022.

In the early years of Canadian Confederation, health was still considered primarily a municipal rather than provincial matter.

The board reported to the Lieutenant Governor (1882-1903), to the Provincial Secretary (1904-1918), then to the Department of Labour (1919-1924).

The department also had responsibility over areas that are no longer associated with health, such as water and sewage functions (prior to 1957), mental retardation facilities and children's services (transferred to the Ministry of Community and Social Services in 1974), and occupational health (transferred to the Ministry of Labour in 1976).

In 1961, the Royal Commission on Health Services, chaired by Justice Emmett Matthew Hall, was appointed, which served as a catalyst for a major overhaul of the department.