La Crosse and its residents have long had an association with aviation that started very early in the Aviation Era. It was only a short eight years after the Wright brothers' first took flight in December 1903 until La Crosse area residents' had their first airplane flight. In October 1911, Hugh Robinson, a regional daredevil gave a flying demonstration to people who had gathered at the local fairgrounds.  Robinson returned several days later and landed a hydroplane on the Mississippi River to deliver airmail to the city.
The city's first airport, Salzer Field, was established in 1919. The airport was located on the City's south side, at the corner of Losey Boulevard and Ward Avenue, on approximately 80 acres land owned by the Salzer Seed Company. A group of local aviation enthusiasts formed the La Crosse Aero Club. The City and the Chamber of Commerce believed that aviation would catch on and would help bring economic growth to the local area.
On February 9th, 1921, Pilot William Carroll was enroute from Milwaukee to Minneapolis/St. Paul flying the air mail route. Forced to land on the Wisconsin River due to bad weather, Carroll and two members of his crew were killed after their plane experienced an in-flight explosion over La Crosse. This tragedy had national implications. The timing of the crash occurred while debates on the government's role in aviation were occurring. As a result, funding was cut, and only transcontinental air mail routes that ran from New York to San Francisco via Chicago and Denver survived. One of the main points of debate was the ability of the Federal Government to regulate aviation under the guidance of the constitution. The debate was settled in February 1922 when the U.S. Supreme Court ruled on the case of the Wisconsin Railroad Commission, which was the predecessor of the modern Department of Transportation. The Court ruled that the federal government has power to regulate intrastate commerce. In 1925, the Kelly Act was passed, providing subsidies that all but created the American Airline Industry.
In 1926, the City decided to purchase the land known as Salzer Field, thus becoming the first airport in the City of La Crosse. Shortly after, Northwest Airlines began the first commercial service to La Crosse. In 1932, the City, having difficulty maintaining the airport because of large demands for modernization, abandoned Salzer Field on July 13, 1933. 
That same year, the La Crosse County Board of Supervisors leased a field on French Island to serve as a new airport. While initial work and progress on the airport was slow, a Depression Era "New Deal" program designed to put people to work allowed progress at the new airport to continue. The new two-runway field, known as Pfafflin Field, was dedicated as the new County Airport on August 18, 1935.  Control of the new airport, however, was not assigned to the county. A contract was negotiated by the county and Ray Pfafflin for Pfafflin to operate Pfafflin Field for a period of five years after which the county then had the option to purchase. The County Park Commission purchased the land for $14,141. After Raymond Pfafflin filed an appeal with the Wisconsin Supreme Court, the county decided to give up its attempt to develop and run the airport if Mr. Pfafflin would drop his appeal.
A requirement of receiving federal airport funds is for the airport land to be publicly-owned. The City of La Crosse finally purchased Pfafflin Field in February 1946, and it became city property. The La Crosse Municipal Airport, a class IV airport, was dedicated on March 1, 1947. Northwest Airlines began scheduled air service the same day with five daily flights. The three asphalt runways at the new airport were 5299 ft. x 150 ft. The city, recognizing that continuous improvement was required, built a new terminal building in 1953.
The city hired Socony-Vacuum Oil Company, Inc., to develop a "general plan" for the La Crosse Municipal Airport. Impressed with the location and layout of the airport, the consultants devised three stages of development.
The first stage consisted of building T-hangars, a large hangar, and refueling facilities, and also recommended sizes, designs, and locations for these structures. The T-hangars would solve the initial problem of having space for transient and based airplanes that must be hangared overnight. The large hangar could and should serve as an administration building until activity at the airport increased to the point where a separate administration building was required.
The second and third stages of development included building other hangars when traffic warranted and hiring a director to manage the airport.
Air service continued to improve at the La Crosse Municipal Airport as the establishment kept pace with the ever-increasing requirements to safeguard all persons that utilized the aviation system. These improvements included wind indication devices, improved lighting systems, improved communication systems, emergency back-up electrical power, better snow removal equipment, security fencing, maintenance storage buildings, and a terminal building.
By 1975, the city had built a terminal building to accommodate the traveling public. There were two fixed-base operators to provide necessary aviation services, an air cargo facility, various corporate flight facilities, and seven T-hangars.  La Crosse Airline Service was provided by North Central Airlines with a combination of Convair 580 and DC 9 jet aircraft and by Mississippi Valley Airlines with Metroliners and DeHavilland Otters. Viking Aviation, Inc., La Crosse Flite Center, and Viking International Airlines provided charter flights and air cargo services. In 1974, the La Crosse Municipal Airport was the fifteenth largest employer in the La Crosse area, paying over $1.4 million in wages.
By 1990, the airport had grown to approximately 1,380 acres including a new terminal building, located on Airport Road. In conjunction with the new terminal building, an Airport Industrial Park was developed. The airport was and is a modern all-weather capable facility.
In August of 2013 the La Crosse Municipal Airport was renamed the La Crosse Regional Airport to better represent the geographic area the Airport serves.
In February 2016 the La Crosse Regional Airport Terminal Rehabilitation Project was dedicated with a nearly $14.2 million dollar renovation project.
Today, the airport sits on 1,380 acres of land and supports approximately 19,000 operations every year. The original runway layout is still in use, but many improvements have taken place over time. Two of the runways have seen expansion to 8,742 feet and 6,050 feet. At 8,742 feet, the La Crosse Airport has the third longest runway in the state of Wisconsin with Milwaukee having the longest and Madison the second longest.
With its infrastructure, the La Crosse Airport can accommodate even the largest aircraft in service today. The airlines process nearly 90,000 enplanements and 180,000 total passenger annually.
The La Crosse Airport is a self-sufficient entity of the City of La Crosse; taxpayer dollars do not go into the operating budget of the airport.
The staff at the airport consists of 13 city employees; of whom four are trained Operations Coordinators who perform ARFF and six are airport maintenance personnel who take care of the airport facilities.