The Municipality of Santa Maria lies in the central part of the Province of Bulacan approximately within the longitudinal coordinates of 120°56'30.85"E and 121°1'54.02"E and within the latitudinal coordinates 14°47'8.90"N and 14°54'2.20"N.

It is a landlocked town along with several lowland and central municipalities of Bulacan. It is accessible by land via the North Luzon Expressway and Manila North Road or MacArthur Highway, which is about 700 meters and 2.3 kilometers away from the town respectively.

There are five (5) municipalities and one (1) city surrounding the municipality of Santa Maria. These are the municipalities of Angat and Pandi on the north, municipality of Norzagaray and City of San Jose del Monte on the east, municipality of Marilao on the south and municipality of Bocaue on the west.