Judge Roy Hofheinz, who was one of the original owners of the Houston Astros baseball team and spearheaded the lobbying effort that resulted in Harris County financing the construction of the Astrodome, founded the "Astrodomain" holding company after the Astrodome's opening in 1965. It owned 116 acres (47 ha) in south Houston surrounding the Astrodome. Hofheinz continued to develop the Astrodomain, creating AstroWorld (1968), the Astrohall convention center (which hosted twice-daily stagings of the Ringling Bros. and Barnum & Bailey Circus in 1969; Hofheinz had acquired the circus in December 1967), and four hotels with a capacity of 5,600 guests to serve visitors: the Astroworld Motor Hotel (with a private suite for Hofheinz on the ninth floor), Holiday Inn-Astroworld, Howard Johnson Motor Lodge-Astroworld, and Sheraton Inn-Astroworld.

In 1967, Hofheinz initially denied that preliminary work for an amusement park had been underway, but later announced on September 16 that approximately half of the remaining land, 57-acre (23 ha), was being developed for a park to be named "Astroworld". Hofheinz showed an architectural model of the park and announced that Randall Duell and Associates had designed it; Duell, a Hollywood set designer and architect, had previously designed Six Flags Over Texas. An initial $25 million investment paid for extensive landscaping and a long pedestrian viaduct spanning the I-610 freeway, the first privately owned, publicly accessible span over a federal highway. Lloyd, Morgan & Jones designed the bridge.

Additional design work for the park was performed by I. A. Naman & Associates (air conditioning); Lockwood, Andrews & Newnam (electrical); Walter P Moore (structural); Turner, Collie & Braden (civil engineering); and Linesch & Reynolds (landscape architects). 500,000 cu yd (380,000 m3) of fill was required for the site, because of its low elevation and drainage issues. Dozier Specialty, who had previously worked on Colt Stadium, was the general contractor. The name AstroWorld was selected following Houston's designation as the home of the Johnson Space Center in 1965, paying homage to the nation's crewed space programs.

Executives commissioned Ed Henderson, a Disney animator, to build a scale replica of the park and design maps for park guests. Henderson's model of AstroWorld, measuring 8 by 10 feet (2.4 m × 3.0 m), was built as a publicity preview of the park in 1967. Architecture students at Rice University and the University of Houston sculpted many of the buildings. It was displayed in the window of Foley's, a downtown department store, then moved to Hofheinz's Astrodome suite once the park opened; as an Easter egg, a model of Hofheinz's black Cadillac is parked in a private lot in the northwest corner of the park's model. After the park closed in 2005, the model was discovered, sawed into six pieces in a warehouse, then returned to Henderson. He stored it in his garage before it was displayed in fall 2010 at the Optical Project gallery, operated by artists Bill Davenport and Francesca Fuchs. In 2011, it was sold to I. A. Naman and Associates, the same firm that had designed the park's outdoor air conditioning; they donated the model to the Houston Public Library.

The Hofheinz family, Roy and his three children (Roy Jr., Fred, and Dene), shared ownership of the park. Hofheinz hosted a press preview in May 1968; Leonard Traube wrote the park "has a beautifully realized continuity and layout calculated to move traffic in such a way as to make practical the policy of a single gate admission for virtually everything on the grounds", referring to the Duell loop that routes visitors through each part of the park.: 83 

AstroWorld opened on June 1, 1968, just south of the Astrodome, creating a multi-facility entertainment complex; 50,000 guests visited the park during the first weekend. Hofheinz enlisted two of his grandchildren to launch the amusement park with the release of 2,000 balloons. An initial workforce of 1,200 collected tickets at a price of $4.50 for adults and $3.50 for children. Stan McIlvaine, who had formerly operated Six Flags Over Texas, was the first general manager of AstroWorld. Two of the park's sixteen attractions were not operational on opening day.

Marvel McFey, the park's official mascot (branded the "Ambassador of Happiness"), was introduced in 1972. He was accompanied by a menagerie of "animal gypsies": Winston Wolf (the sheriff of AstroWorld); Pigs One, Two, and Three (mischievous tricksters named Quiz, Chiquito, and Harpo); Percy Penguin; Pierre Le Rat (the resident artist); Flopper Rabbit (a country bumpkin); Beethoven Bear (a checkers champion); Samantha Skunk ("a bright purple and pink flower child"); Frieda Frog (McFey's secretary); and Lester Lion (a frustrated baseball player). In addition to their in-park greeting and show duties, Marvel and his caravan of Enchanted Animals represented AstroWorld at many civic functions. Rolly Crump designed and built the character costumes.

In 1970, just two years after the opening of Astroworld, Hofheinz survived a stroke that left him in a wheelchair. The enterprise announced a $38 million long-range financing program in 1972, with notes held by General Electric Credit Corp., Ford Motor Credit Co., and HNC Realty. Those creditors assumed control of the Astrodomain in 1974. Astrodomain sold the hotels to Servico Inc. in May 1976. Hofheinz liquidated his interest in the company a short time later.

Six Flags purchased a 20-year operating lease for AstroWorld in mid-1975. The following year, Six Flags AstroWorld introduced a new, high-speed roller coaster, the Texas Cyclone. A new playground named "The Magical World of Marvel McFey" was added to Children's World for the 1977 season. That same year, Robert Cartmell named the Texas Cyclone the best roller coaster in the world. The formal purchase of AstroWorld by Six Flags concluded in 1978. In 1978, the new attraction was Greezed Lightnin', a high-acceleration loop roller coaster.

McFey's tenure as the park's mascot ended in 1984 as Bugs Bunny and other Looney Tunes characters moved into the Enchanted Kingdom for the 1985 season; AstroWorld's parent corporation, Six Flags, had acquired the license to use the Looney Tunes characters in 1984 for its theme parks from Marriott along with the Great America in Gurnee theme park; Marriott had held the license since 1976 for its twin Great America parks.

Six Flags continued to change ownership, being purchased by Bally Manufacturing in 1982, then by a private equity firm, Wesray Corporation, in 1987. Time Warner acquired a minority stake in 1990 and owned the company outright by September 1993. During Astroworld's first twenty years, it entertained more than thirty million visitors. The amusement park persisted while new competitors in Houston emerged and failed, including Busch Gardens, Hanna–Barbera Land, and SeaArama Marineworld. Attendance increased during these earlier years. In the early 1990s, the Six Flags parks gained access to DC Comics characters through its corporate owner, Time Warner; Batman: The Escape was installed at AstroWorld for the 1993 season. In February 1998, Premier Parks, led by CEO Kieran Burke, acquired Six Flags Entertainment Corporation. In 1984, Premier, originally Tierco, a property management group, hired Gary Story to rehabilitate one of its properties, an older park named Frontier City in Oklahoma City; Story's successful turnaround of that park started the company's theme park acquisition program.

The Six Flags acquisition was part of an ambitious Premier Parks purchasing program, which bought 31 amusement parks in four years, including the 12 Six Flags parks. Burke received a $2 million bonus for completing the Six Flags acquisition. However, Six Flags failed to turn a profit for five straight years after the 1998 acquisition, announcing a $122 million loss for the first half of 2003; capital expenditures began to be scaled back because of its debt load. In August 2005, Six Flags announced it was selling its chain of parks. One month later, on September 12, Burke announced AstroWorld would be closed and demolished at the end of the 2005 season. The company cited issues such as dwindling attendance, rising property value, and conflicts involving off-site parking at Reliant Stadium, which houses the Houston Texans football team and the Houston Livestock Show and Rodeo (HLSR). In 1997, the combined attendance of AstroWorld and Water World was 2.27 million visitors; AstroWorld alone was ranked as the 28th most attended theme park in the United States with 1.99 million guests. AstroWorld attendance ranked 35th overall among all theme parks in 2000, 37th overall in 2002, 36th overall in 2003, and 39th overall in 2004, which was eighth among all Six Flags parks in 2004. A contractual agreement that allowed Six Flags patrons to park at Reliant Stadium expired in August 2005, and attempts to extend it failed. CFO Jim Dannhauser cited the expired parking arrangement as a "contributing factor" in the decision to close. Burke later explained in 2014 the decision was based on " condition and location and the costs to modernize ... we had big offers pouring in for the land at the time and it just made more sense to close it." The final date of park operation was October 30, 2005. Following the closure, most of the park's assets, including rides and equipment, were sold during a three-day public auction held January 6–8, 2006.

Company executives expected to sell the land for as much as $150 million, but ultimately received less than half that amount. After spending $20 million to demolish the park and clear the land, Six Flags sold the cleared property for $77 million in 2006 to Angel/McIver Interests, a land development firm based in Conroe, Texas. By that time, Burke had been removed as CEO. In 2009, the former Astroworld site was still vacant. The land tract was reported as taking up 104 acres (42 ha). The land owners hired real estate consultants, Croswell Torian Commercial Properties, to subdivide and market the property to other developers under the "SouthPoint" brand, though no development had yet occurred. The original 110-acre (45 ha) tract purchased by Hofheinz was reduced by 8 acres (3.2 ha): 5 acres (2.0 ha) were acquired by Harris County Metro and another piece of the tract on the northwest corner sold to a car dealership.

The Houston Livestock Show and Rodeo (HLSR) are the owners of a record-holding 102 acres (41 ha) of cleared land bounded by West Bellfort Drive, Fannin Street, Kirby Drive, and I-610. The original amusement park site occupied 57 acres (23 ha) of that. Parts of the tract were developed, and other parts were undeveloped; the HLSR was using some of that property for overflow parking and conveying those visitors over the long pedestrian viaduct, the last remnant of the former amusement park. Though the site includes a great field of grass, the land is stabilized and partly paved with asphalt, so it can be used for parking.