Constructed in 1852 and operated until 1905, the Point Isabel Lighthouse was built to protect and guide ships through Brazos Santiago Pass and the barrier islands. In 1952, the Lighthouse was opened as a State Park and remains the only lighthouse on the Texas Gulf coast open to the public. The Lighthouse Keeper’s Cottage which is on the grounds of the Lighthouse, is open to the public and houses the Chamber of Commerce and the Port Isabel Visitors Center. There is no admission charge to the Keepers Cottage. Lighthouse tickets can be purchased at the Keepers Cottage or at the Lighthouse.

The Neale House is said to be the oldest frame house surviving in Brownsville, dating to sometime in the 1860s or earlier. It originally stood at 625 East 14th St. but was moved to this location on Neale Road in 1950 by the Brownsville Art League. This location was once part of Fort Brown. The builder of the home was an Englishman named William A. Neale (1807-1897). Neale was a local businessman, Civil War veteran, and served two terms as mayor of Brownsville, from 1858-1859 and 1866-1867. Neale bought the two lots where the house was to be built in the original town of Brownsville in 1850 from Samuel Belden. The house stayed in the Neale family until 1950 when a direct descendant, Mrs. Mamie del Valle, gave the house to the Brownsville Art League.

The Stillman House Museum has been open since the 1960s as a historic house museum after restoration. The Heritage Museum next door opened in 2002 and offers photo displays, exhibits, and interactive displays; it also houses La Tienda Gift Shop and the administrative offices of the Brownsville Historical Association (BHA). The Greek Revival style Stillman House was built circa 1850 and is one of the oldest residences in Brownsville. It was built as the home of Charles Stillman, a wealthy businessman who was one of two owners of the original townsite of nearly 5,000 acres in 1848, along with Samuel A. Belden. The house was owned by the Trevino family from 1858 to 1958 and was home of the Mayor of Brownsville, Thomas Carson, in the 1890s.

The core of the Market building in the center of Market Square was built 1850 - 1852, with multiple arcaded stalls on the ground floor selling fresh fruits and vegetables and City of Brownsville offices on the second floor. A two-story fire department building was built in 1908 - 1909 free-standing on the E. 11th Street (northwest) side of Market Square. The 1850s building was gutted in 1912, the second floor office space above the market stalls was reconstructed, and a two-story extension was built on the front of the building, facing E. 12th Street (southeast side). The first floor stalls were walled off from the outdoors in 1940. In 1948 - 1949 the fire department building was incorporated into the newly-stuccoed Market building. The city bus station occupied the building by the 1980s. Market Square was leased to the Brownsville Historical Association (BHA) in 2009. The BHA Research Center within the building contains a wide range of photographs and documents on local history.

Built in 1859, Immaculate Conception Cathedral is a historic Catholic church located in the heart of Brownsville. It is notable for its elegant Gothic architecture and for the man who designed it, Father Pierre Y. Keralum, who was a trained architect. The church is also a symbol for the development of the Catholicism in Texas. It was built just ten years after Brownsville was established, and was the location of the first permanent settlement in the country of a Catholic order called the Oblates of Mary Immaculate (OMI). The church remains an active Catholic parish and is listed on the National Register of Historic Places.

La Madrileña is one of the more architecturally unique buildings in Brownsville. It was built in 1892 by Spanish native Adrian Ortiz (1860-1957), who became a prosperous merchant and prominent figure in the city. Ortiz, who was born in Madrid, Spain, named the building La Madrileña, which means "native of Madrid." The building is an excellent example of vernacular commercial architecture, featuring a number of interesting elements including elaborate corbeled brickwork, curved parapets, pinnacles, and several pairs of wooden doors set in bays on the street-facing sides of the structure. The building today appears to house a law firm.

The Laureles Ranch House was once the home of Brownsville founder Charles Stillman. The house is a late Georgian Greek revival style frame house that was built for Charles around 1850 on his ranch north of Brownsville and south of Corpus Christi. Charles purchased land on the old Spanish land grant in 1848 from the Perez-Ray family. Charles sold his interest in the ranch to his brother, Cornelius in 1864 and moved to New York with his family. After four years of operating the ranch, Cornelius sold it to Miflin Kenedy. The restored home is now located in Linear Park and is open as a museum by the Brownsville Historical Association. The Laureles Ranch House is available for rental as a rustic venue for special events.

Located inside the Mitte Cultural Education Center in Dean Porter Park, the Costumes of the Americas Museum houses the world's largest collection of traditional, indigenous clothing—as well as accessories such as jewelry and headpieces—from the Americas and the Caribbean. The center and the museum opened in 2005.