Nacogdoches Memorial Hospital opened its doors on Dec. 14, 1928, and was known as City Memorial Hospital. City Memorial was owned by the City of Nacogdoches and had 28 beds. Originally, the city owned its own electrical system, which the City Commission decided to sell. Using the $150,000 profits, they built the hospital on land donated by Mrs. Itasca Blount. In 1928, City Memorial was dedicated in honor of World War I veterans, but now is dedicated to the memory of veterans of all wars.

By an act of the Texas Legislature on June 12, 1967, House Bill #1248 established the Nacogdoches County Hospital District. On April 9, 1968, an election was ordered by the Nacogdoches County Judge, calling for an election to establish ownership of City Memorial by the Nacogdoches County Hospital District. The vote was approved by a substantial majority. On May 6, 1968, ownership transferred to Nacogdoches County Hospital District, the name of the hospital was changed to Memorial Hospital, and the first board of directors was elected.

Additions were made to the facility in 1938 and 1951. Later additions include:
South wing (1964)
Tucker wings (1984)
Emergency room (1982 )
Cardiac catheterization lab (1988)
Rehabilitation unit (1988)
Medical Imaging special procedure room (1999)

Major renovations/updates were made in:
Hospital (1980)
Women's wing (1991)
ICU (1991)
Charles Bright Pavilion (1992),
Lobby (1996)
Admissions (1996)
Labor & delivery (1996)
Cafeteria (1996)
Cardiac catheterization lab (2000)
ICU/IMC, Emergency Room and Physical Therapy Services (2003)