The Houston Museum of Natural Science began in Houston in 1909 with the founding of the Houston Museum and Scientific Society "to establish and maintain a free institution for the people, for education, and for science." In 1914 the group persuaded city officials to buy part of a natural-history collection assembled by Henry Philemon Attwater, and in 1922 the remainder of the collection was bought by Sigmund J. Westheimer and given to the city. The collection, first housed in the city auditorium, was subsequently housed in the Central Library for seven years, and then in a Hermann Park Zoo site, where Val Gesner served as curator. By 1943, after donations from John E. T. Milsaps and others, the collection comprised some 17,000 items. At this time Robert A. Vines became museum curator. The museum was managed by the city park department for more than thirty years after the initial purchases were made, but in 1946 a private nonprofit corporation known as the Museum of Natural History of Houston was formed to assume maintenance and operation. Vines, who was named director and served until 1956, was replaced after a brief interim by Thomas E. Pulley in 1957. The first step toward the present museum was taken in 1959 with the negotiation of a ninety-nine-year lease with the city for a 4½-acre site on the northern edge of Hermann Park. At the same time, the trustees received a gift from Burke Baker, which became the basis for construction of the Burke Baker Planetarium.
In 1960 the museum was officially renamed Houston Museum of Natural Science. The planetarium and a new building designed by Jim Goodwin of Pierce and Pierce, with the consulting firm of Staub, Rather, and Howze, were under construction in 1964; they opened in 1969. A new wing to house traveling exhibits was completed in 1982. Truett Latimer became director of the museum in 1986 and was later named president. Displays at the museum included a dinosaur exhibit, a space museum, and exhibits on geology, biology, petroleum science, technology, and geography. In 1988 the museum became the nation's first affiliate site for a Challenger Center (the Challenger Center is an organization formed by relatives of astronauts on the space shuttle Challenger to further space science). The Wortham IMAX Theatre opened in 1989, as did the George Observatory in Brazos Bend State Park. Museum representatives served the Houston public schools by teaching science classes and also provided information to the public at large.
In 1990 museum attendance was more than one million visitors. That same year, trustees of the Houston Museum of Natural Science reevaluated the museum's status to develop a five-year action plan and decided that new state-of-the-art facilities, additional space, and renovations to current exhibits were needed because of increased attendance. In 1991 renovations began on the Isaac Arnold Hall of Space Science and the McDannald Hall of the American Indian. The museum also launched its "Face of the Future" campaign to build a 90,000-square-foot exhibit wing. Renovations continued through the 1990s. With the aid of campaign funds, the Houston Museum of Natural Science made improvements to the Welch Chemistry Hall in 1993 and the Paleontology Hall in 1994. The Cockrell Butterfly Center and the Brown Hall of Entomology opened in July 1994. The expansion of the Sterling Hall of Research was completed and the Wiess Energy Hall was reopened.
The year 1995 saw an expansion of the gem and mineral collection, with two acquisitions from private collections—the first from New Jersey’s Ed and Ann David Collection and the second from the Bernus-Mane Collection from Spain. These acquisitions resulted in a total renovation of the Cullen Hall of Gems and Minerals into a permanent exhibit, bringing it world-class recognition. Burke Baker Planetarium, the museum's original venue, was renovated to include a seamless dome, tilted seats, and a modified sound system in 1998. In 1999 the Albert and Ethel Herzstein Hall of Special Exhibitions opened, featuring traveling exhibits on loan from premier collections throughout the world.
Truett Latimer, museum president, resigned in 2001 after a fifteen-year term, and Rebecca A. McDonald was named the new president later that year. After serving a little over three years, McDonald resigned her presidency, and Joel A. Bartsch became the seventh president of the museum. By 2006 the Houston Museum of Natural Science had more than two million visitors each year. Four floors of permanent exhibit halls contained more than one million objects and specimens, with additional touring exhibitions throughout the year. In 2007 the museum opened the Woodlands Xploration Station, a satellite educational facility, and in 2008 the museum entered into an agreement with the city of Sugar Land to open a satellite education facility there.
By 2010 the museum was in the middle of another major expansion on an adjacent acre and a half of real estate. As part of the expansion plan, the museum paid $5 million to the Hermann Park Conservancy, which oversees the 445-acre urban park situated between the museum district and the Texas Medical Center in Houston. The funds served to extend the museum’s lease and allowed for access to the additional land for expansion.