Midtown is a district southwest of Downtown Houston, bordered by Neartown, U.S. Highway 59 and Interstate 45.

Around 1906 what is now Midtown was divided between the Third Ward and Fourth Ward.Before the 1950s what is now Midtown was a popular residential district. Increasingly, commercial development lead homeowners to leave for neighborhoods they considered less busy. The area became a group of small apartment complexes, low-rise commercial buildings, and older houses. According to a City of Houston report, the remaining churches and the Houston Community College System Central campuses provided the neighborhood’s “only stability.”

In the 1970s, Midtown became home to Little Saigon, a neighborhood of Vietnamese and Vietnamese Americans, who pioneered the redevelopment of Midtown Houston. During the 1980s, Travis and Milam Streets were viewed as a mirror image of 1970s era Saigon. The Vietnamese areas were established around Milam Street, Webster Street, Fannin Street, and San Jacinto Street.  On June 24, 1994 Isabella Court at 3909-3917 South Main Street received listing in the National Register of Historic Places.

The City of Houston established the Midtown Tax Increment Reinvestment Zone (TIRZ) in 1995.The establishment of the TIRZ lead to the opening of upper income townhomes and apartment complexes in western Midtown and the area along Elizabeth Baldwin Park. Between 1990 and 2000 the area within the Midtown neighborhood saw the population increase from 3,070 to 5,311. The increase by 2,241 people was 73% of the 1990 population. During that period about 2,200 multi-family units opened, particularly along Louisiana Street and West Gray Street. Since the total multi-family acreage remained at a small number, the population increase also increased the density of the area. During the 1990s commercial uses increased, particularly along Main Street and Louisiana Street. In 1999 the 76th Texas Legislature created the Midtown Management District.

By 2004, higher rents and street construction have reduced the number of Vietnamese American businesses, many of which have relocated to the outer Houston Chinatown in the Bellaire Boulevard corridor west of Sharpstown. On May 1 of that year, during the 6th Annual Asian Pacific American Heritage Month Festival, the section of Midtown along Milam Street and Travis Street near Tuam Street received the designation “Little Saigon.”

In 2009 Houston City Council approved the expansion of the Midtown TIRZ by 8 acres (3.2 ha). The new territory includes the Asia House, the Buffalo Soldiers Museum and the Museum of African-American culture.