After World War I, the idea of opening an airport in the Roanoke Valley became a priority for local leaders. The intended purpose was to provide a landing strip, aircraft storage, and a flight school. The original location was 6 miles (9.7 km) north of Roanoke city limits in Roanoke County. The location was secured on July 1, 1929, when the city of Roanoke signed the lease on the land to operate the Roanoke Municipal Airport. The original facility had a single 83 feet (25 m) x 100 feet (30 m) hangar and a pair of dirt runways. The first airline service commenced in 1933 when Ludington Airlines made Roanoke a stop on their New York to Nashville route.

By 1934, American Airlines began service to Roanoke, but they moved their operations to Lynchburg in 1937 due to poor conditions in Roanoke. After American's withdrawal, city leaders determined a new facility was needed. It was initially privately operated, but the city of Roanoke took control of the facility in 1937 after it purchased the original hangar, with Works Progress Administration funds paying the costs of paving the runways. After the airport was declared a national defense project, federal funds became available to complete the facility. On December 15, 1941, it was officially dedicated. The airport was named Woodrum Field in honor of Clifton A. Woodrum, the congressional representative from Virginia's Sixth District, and after it reopened, American Airlines reestablished service to Roanoke Municipal Airport.

In 1950, Roanoke had three runways: 3730-ft runway 5, 3910-ft runway 9, and 4270-ft runway 15. By 1962, runway 5 had been extended to 5427 ft, and by 1965, runway 15 was 5800 ft; there was no further change until runway 9 was closed around 1970. In 1981, runway 5 was the longest, at 5903 ft.

The first airline jets were Piedmont 727s in 1967.

Shortly after it departed from Asheville Regional Airport in Asheville, North Carolina, on July 19, 1967, Piedmont Airlines Flight 22 collided with a Cessna 310 on approach to Asheville. The Piedmont Boeing 727 was en route to Roanoke. There were 82 fatalities and no survivors, making this the deadliest accident associated with Roanoke Regional Airport.

A proposal for runway expansion and facilities upgrades was developed in 1975 but was put on hold while a new regional airport was being studied. During this time, airline deregulation was put in place, and this, combined with the airport's aging facilities and airlines' phasing out of turbo prop aircraft, resulted in less service to the airport. a runway expansion began in the early 1980s to allow larger jets. With the runway extension underway, the airport changed its name from Roanoke Municipal Airport to Roanoke Regional Airport in 1983. The runway expansion was completed in 1985.

In 1984-85, the city developed a Master Plan calling for $43.8 million to be spent on a new terminal building and other improvements. $15.4 million was secured in state and local authorities covered local funding, and the remainder. The creation of a Regional Airport Commission to oversee airport operations was proposed to cover this funding. Approved by the Virginia General Assembly on February 18, 1986, and initiated on July 1, 1987, the Roanoke Regional Airport Commission has five members, three appointed from Roanoke City and two from Roanoke County. The commission ended the city of Roanoke's role as the sole operator of the airport, as it had been from 1934 through 1987.

Roanoke has never had international passenger service, but in 2001 the Airport Commission was prepared to change the airport's name to Roanoke International Airport. This was the case as the U.S. Customs Service increased the radius covered by the inland port in Dublin to include Roanoke. This expansion allowed the airport to add customs officials to accommodate international travel and cargo passing through Roanoke. The renaming did not occur as a result of the economic downturn in the wake of the September 11, 2001 attacks, however. In 2007, the prospect of changing the airport's name was again proposed by the Airport Commission.

Residents and businesses have been known to take issue with the airport's limited non-stop flights and lack of low-price fares. Airport officials estimate that around a third of airline tickets purchased by area residents are for travel from other airports. Competition includes Piedmont Triad International Airport near Greensboro, North Carolina, and others farther away that have service from Southwest Airlines or international flights. Aviation industry consultant Michael Boyd compared Roanoke's level of air service favorably to similarly sized cities.

The airport added non-stop service to Orlando in May 2006 and Tampa in December 2006 with Allegiant Air. This was part of an effort to bring new and improved service to the airport with existing and new carriers. Earlier attempts to lobby AirTran Airways and the now defunct Independence Air to serve the airport were unsuccessful.

Airlines

Airline service to Roanoke commenced in 1933.