Weslaco, about fifteen miles west of Harlingen in south central Hidalgo County, is on U.S. Highway 83 and Farm Road 88. The site was part of the Llano Grande grant to Juan José Ynojosa de Ballí (1790). Upon Ynojosa's death the grant was divided among his children, and Manuela and María received the land on which Weslaco is situated. The Ballí family ranched and maintained ownership until 1852. In 1904 the Hidalgo and San Miguel extension of the St. Louis, Brownsville and Mexico Railway reached the site, promoted by Uriah Lott, Lon C. Hill, Jr. and others interested in developing the area through farming as opposed to traditional Hispanic ranching. The American Rio Grande Land and Irrigation Company of neighboring Mercedes, which had interest in the railroad, purchased a major portion of the Llano Grande grant and platted the West Tract in 1913. In an effort to control raids from Mexico, the United States government stationed troops along the Rio Grande in 1916 and established a camp at the Llano Grande railroad depot, located between Mercedes and the site of Weslaco. The guardsmen erected a watchtower at Progreso. On December 14, 1917, the irrigation company sold 30,000 acres at ninety dollars an acre to the W. E. Stewart Land Company, from which the name Weslaco is derived. The Stewart Company sold the townsite to Ed C. Couch, Dan R. Couch, R. C. Couch, and R. L. Reeves. The site was surveyed and platted on September 18, 1919, by H. E. Bennett, a civil engineer hired by Ed Couch and R. L. Reeves, whose partners had backed out of the venture in fear of failure. Neighboring communities distributed leaflets discouraging settlement at the proposed town. Nevertheless, the sale of lots was held on December 8–10, 1919, with prices ranging from $50 to $400 per lot. To make a claim, individuals had to choose a lot and camp on it until the day of the sale, during which lots were given free to church groups. The town's promoters gave away three cars during the sale. Mail in Weslaco was received from Mercedes until 1920, when Weslaco's first post office was opened. Also established in 1920 were the chamber of commerce, the Guaranty State Bank, and the Community House. Elementary school classes were held at the Community House, and high school students were driven to Donna. The first issue of the Weslaco News was published on October 29, 1920. Electricity came in December 1920 from the Donna Light and Ice Company. In 1921 the Weslaco Independent School District was established, the first high school opened, and the Texas Rangers opened a Weslaco station. The Valley Experiment Station was established in 1923 under the auspices of Texas A&M. It was later renamed Texas A&M University Agricultural Research Center. The Weslaco Fire Department was established in March 1924.
A municipal ordinance of 1921 provided that the land north of the railroad tracks be designated for industry and Hispanic residences and businesses. The area to the south of the tracks was reserved for Anglo residences and businesses. This segregation was a consequence of the farm culture that had introduced the railroad. Weslaco developed as two cities. "El pueblo americano," as the Anglo side of town was called, consisted of well-built frame houses; it had paved streets and enclosed sewers. The Mexican side featured corrugated tin shacks, unpaved roads, and outhouses. Mexican women were supposed to shop on the Anglo side of town early on Saturdays only, and be back in "Mexican Town" by sunset. Streets north of the tracks had Spanish names, business was conducted in Spanish, and schools were established for Mexican children. In "American Town," streets were named for northern states. In the 1928 county election the Weslaco ballot box was rejected by Judge A. W. Cameron, an incumbent official whose victory was in question. Cameron, who evidently believed that he would have won the Hispanic vote of Weslaco, testified that Mexican-American voters had been intimidated by a crowd yelling "Don't let those Mexicans in to vote. Throw them out." The protesters were allegedly led by the Citizens Republican Committee. Only years later did Mexican Americans throughout South Texas became powerful in local politics.
Construction of a railroad depot in 1927 attracted canning plants, dehydrating plants, and a box factory to Weslaco. A ground-level water reservoir was constructed in 1928. The first Weslaco "Birthday Party" was held in December 1929 and included a parade and style show. By 1930 the town's population had reached 5,300. In 1936 civic plans required all buildings in the business section to be remodeled with Spanish colonial architecture. Weslaco then acquired the nickname "City with the Neon Skyline" because neon lights were used to outline the new facades. In 1936 the Gibson Trailer Campground opened; at the time it was the only municipal campground for tourists in the lower Rio Grande valley. The overhead tank for the Weslaco Water tower was constructed by the Work Projects Administration between 1938 and 1941. In 1939 the United States Farm Security Administration established a camp north of town on what is now Highway 83. The $250,000 camp, the first of its kind in Texas built expressly for the purpose of housing migrant farmworkers, became known as Weslaco North. The United States Fruit and Vegetable Products Laboratory conducted an experimental tract near the city. By 1940 the Weslaco had an estimated 5,300 residents and 183 businesses. The Weslaco Citrus Growers Association was organized in 1940. That year Weslaco reported a senior and junior high school, a grammar school, a "Mexican and Negro" school, and a Seventh-day Adventist school. Cpl. Harlon Henry Block of Weslaco helped raise the flag on Iwo Jima and was killed during the campaign; a city park in southwest Weslaco was named in his honor. The Gibson Trailer Campground was closed when the privately owned Weslaco Trailer Park was opened in 1945. During the 1947–48 season Weslaco was one of nine Texas communities that handled more than 2,000 carloads of produce. The Texas A&I Citrus Center opened in 1948; experiments there yielded popular varieties of grapefruit. In 1950 the population of Weslaco was estimated at 6,883, served by 220 businesses. An international bridge at the Progreso crossing south of Weslaco opened on November 11, 1954.
Work was begun on an underground drainage and a sewage disposal system for Weslaco North in 1954. From 1964 to 1969 Weslaco North's population was enumerated separately from that of Weslaco proper. Its estimated population was 1,049 in 1964 and 1,150 in 1969. The Weslaco population in 1960 was 15,649. Weslaco schools were officially integrated in 1961. Hurricane Beulah caused $100,000 in damage to the city when it struck the Valley in 1967. In the late 1960s Weslaco reported nine schools, thirty churches, two banks, a hospital, a library, a newspaper, a radio station, and a television station. The town continued to be a centrally located citrus and vegetable marketing and processing center in the 1960s and 1970s. Its industries centered on agricultural businesses, with some cattle feeding and clothing manufacturing. Experiment and laboratory operations of Texas A&M, Texas A&I (now Texas A&M University at Kingsville), and the United States Department of Agriculture were located in Weslaco. In 1970 the population was 15,313. The city reported about 275 businesses in 1973. The migrant "camp" was renamed Northside Apartments in the early 1990s, when it comprised 289 units. Weslaco's population was 21,877 in 1990, by which time the city was part of a complex metropolitan area along U.S. Highway 83. In 2000 the population was 26,935.
Weslaco is surrounded by many colonias, including Sun Country Estates, Expressway Heights, Sunrise, and Sunrise Hill. The estimated combined population of these four was 1,600 in 1986, when they consisted of about 355 dwellings.