Great Mills is an unincorporated community and populated place in St. Mary's County, Maryland, United States. It is located in southern St. Mary's County near Lexington Park and Naval Air Station Patuxent River. Great Mills High School, located on Great Mills Road, opened in 1929 and is described by St. Mary's County Public Schools as the oldest high school in Southern Maryland.

Great Mills is located near St. Mary's City, which was established in 1634 as Maryland's first capital. St. Mary's County, established in 1637, was the first county in Maryland.

The Maryland Inventory of Historic Properties records the Great Mills Farmhouse ruin, also known as the Medical College site, on Flat Iron Road in Great Mills. The Maryland Historical Trust describes the site as one of the earliest known sites associated with the study of medicine in St. Mary's County.

St. Mary's County is associated with several Medal of Honor recipients from the American Civil War. James H. Harris, who served in Company B of the 38th U.S. Colored Infantry, is accredited by the Congressional Medal of Honor Society to Great Mills. William Henry Barnes, born in St. Mary's County, served in Company C of the same regiment and also received the Medal of Honor for actions in Virginia in 1864.

The nearby United States Colored Troops Memorial Monument in Lexington Park honors Union soldiers and sailors from St. Mary's County, including Barnes and Harris. St. Mary's County Government identifies the U.S. Colored Troops Interpretive Center as part of a trail between Lexington Manor Passive Park and John G. Lancaster Park that includes interpretive panels on Civil War-era African American history in the county.

Great Mills does not have a municipal government of its own. In Maryland, municipalities are self-governing cities or towns, and St. Mary's County has one municipality, Leonardtown. For much of Maryland, local government is typically provided at the county level.

County planning documents identify the Lexington Park Development District as the principal growth area for St. Mary's County and describe the 2010 urbanized area as including Lexington Park, Great Mills, and California in St. Mary's County. Naval Air Station Patuxent River, located near Lexington Park, is the county's largest employer and is home to the Naval Air Systems Command and the Naval Air Warfare Center Aircraft Division.

Great Mills Road, also designated Maryland Route 246, connects Great Mills with Lexington Park and the entrance area of Naval Air Station Patuxent River. Public facilities in the community include the Great Mills Swimming Pool on Great Mills Road and the Loffler Center at Chancellor's Run, located within Chancellor's Run Regional Park.