The airline was established on May 3, 1973, in Jamestown, Chautauqua County, New York, USA, and started operations on August 1, 1974, using two 15-passenger Beechcraft 99 turboprop commuter aircraft.

In 1986, Chautauqua Airlines was purchased by GAC, an affiliate of Guarantee Security Life Insurance Company, and added twelve 30-passenger Saab 340 aircraft to replace slower Shorts 3-30s in the fleet.

[4] In April 2010, the Federal Aviation Administration proposed a US$348,000 fine against Chautauqua Airlines for allegedly not performing required inspections for three years.

[5] The FAA alleged that the airline flew an Embraer 145 jet for 43 days past the time one of its inertial navigation units should have been replaced.

In October 2012, Republic Airways Holdings reworked a deal with partner Delta Air Lines, part of the company's broader effort to trim costs and boost revenue amid a decline in demand for regional airline service, to operate seven additional 50-seat Embraer 145 planes under the Delta Connection brand.

Specifically, it would not renew its contract with United Airlines to fly ERJ-145s out of Cleveland and that it would ground all 14 ERJ-145s on April 1, in response to a shortage of qualified pilots.

On July 28, 2014, Republic Airways Holdings announced that Chautauqua Airlines would be absorbed into Shuttle America "by year-end" to reduce costs.