It was founded as a barrio of Bocaue in the early 17th century until it was established as an independent municipality on November 26, 1793, by the Spanish friar Francisco Dominguez Javier OFM.

Known before as Santa Maria de Pandi (Tagalog pronunciation: [pɐnˈde]), it is named under the patronage of the Immaculate Conception (also known as La Purisima Concepcion).

[8] Santa Maria was the home town of José Corazón de Jesús, a Filipino poet popularly known as "Huseng Batute", who started composing his verse as a child.

Another native of Santa Maria is Francisco Santiago, a composer who wrote "Nasaan Ka Irog" and other kundiman songs.

Before the Spaniards came to the Philippines, Santa Maria was just a vast wilderness, inhabited by wild animals and covered by thick and lush rainforests.

Civil affairs started to take shape and the appointment of the first Capitan del Barrio, Andres dela Cruz, paved way for the permanent establishment of Poblacion, which was the seat of Spanish colonial government.

People from other nearby places such as Balagtas, Pandi, Santa Maria, and San Jose del Monte, paid their rents in this convento.

It was during Halili's term as provincial governor when the Capitol building at Malolos was heavily damage due to the aftermath of World War II.

He decided to take over and resurge Casa Real de Malolos as a temporary Gubernatorial Office during the period when the Capitol building was severely damaged.

During the Japanese Occupation, Dr. Teofilo Santiago, dubbed as Dr. Kamoteng Kahoy for his widespread campaign among the town's citizenry to plant cassava, became mayor of Santa Maria.

Santiago was also responsible for the launching of the poultry industry – a livelihood project which earned for the town the distinction of being "The Egg Basket of the Philippines".

From the American colonial rule until the restoration period after World War II, Santa Maria was administered by 12 Presidentes from 1899 to 1937 and 4 Alcaldes from 1938 to 1947.

After the People Power Revolution in February 1986, President Corazon Aquino appointed Dr. Alfredo Perez, who was then the vice mayor of the town, as Officer-in-Charge of the municipality until May 1986, when he was replaced by Ricardo Nicolas, Jr.

In the 2001 elections, Nicolas ran for Representative of the 4th Congressional District of Bulacan and won a landslide victory with more than 80,000 votes over her closest rival.

This area covers the barangays of Silangan, Mag-asawang Sapa, Pulong Buhangin and some parts of Balasing with landscape ranging from 8 to 18 percent slope.

[9] There are 18 barangays with low susceptibility to flooding in the municipality (Manggahan, Santa Cruz, Cay Pombo, Caysio, Pulong Buhangin, Mag-asawang Sapa, Silangan, Balasing, Parada, Tumana, Mahabang Parang, Bulac, Catmon, San Vicente, Camangyanan, Tabing Bakod, Buenavista and San Gabriel).

Basically agricultural, about 29.02 square kilometres (11.20 sq mi) or 30.54% of the town's land area is devoted to crop production.

Quarrying has become a significant means of living for the local population, where the abundant pyroclastic deposits from the Guadalupe Formation, such as tuff and ignimbrite in Santa Maria, are quarried for construction and decorative purposes.These valuable resources are indispensable in numerous sectors, such as construction, infrastructure development, and artistic pursuits.

Wind coming from the Pacific Ocean is generally blocked by the Sierra Madre mountain range, a few kilometers east of the municipality.

The Members Church of God International, or popularly known as Ang Dating Daan, has multiple coordinating centers or locales in the municipality, namely: Poblacion, Balasing (located in Pulong Buhangin near their border), Bulac, Cay Pombo, Caysio, Gardenville (Pulong Buhangin), and Parada.

For example, the locale of Bulac has members from nearby Catmon and Sapang Palay Proper (San Jose Del Monte City).

This will provide for the clustering of lower density land uses to help meet housing, employment and public services needs of the people.

Its rapid population growth contributes largely to the establishment of more commercial and trading activities as some people see this as an opportunity for business.

Santa Maria is home to ten resorts located in barangays Pulong Buhangin, Balasing, Catmon, Bulac, Mahabang Parang, Tumana and Lalakhan.

These resorts have become the main destinations of the residents from Metro Manila and Santa Maria's nearby towns for their leisure and summer experience.

Facilities like swimming pools, convention/seminar rooms, hotel, cottages, and spacious parking spaces that could accommodate fifty buses at a time equipped these resorts.

Most notable during the month of February is the availability of "Tuge", a ready to eat root crop sold by vendors that signify the ambiance of the festivity together with the cool breeze which last right after the celebration of the town fiesta.

The most common sports and recreational facilities in the town are basketball courts located in school compounds and in other part of 24 barangays.

A tennis court and a gymnasium named after the late Ricardo D. Nicolas, Jr. was constructed at the FFHNAS campus in Barangay Guyong.

Services range from simple to major surgeries, microchip implantation, vaccinations, laboratory works, confinements, emergency cases, and grooming.