Skybus Airlines Inc. was a privately held airline based in Columbus, Ohio, United States. It operated as an ultra low-cost carrier modeled after the European airline Ryanair, and aimed to be the least expensive airline in the United States. The business model was heavily reliant on flying routes where other airlines did not have direct flights, as Ryanair did in Europe, thus keeping competition to a minimum, and on flying into secondary airports, rather than heavily trafficked ones. The airline also sold advertising space on the interior and exterior of its aircraft, as well as selling merchandise on board. Skybus applied for operating approval on January 1, 2005, received approval to operate on March 15, 2006, and FAA certification on May 10, 2007. It had been granted a waiver to begin ticket sales on April 24, 2007; Skybus' first passenger flights out of Columbus began on May 22, 2007. Less than a year later, Skybus announced on April 4, 2008, that it would cease operations as of April 5, citing the lagging economy and rising fuel costs as causes.

Taking advantage of America West Airlines pulling down its Columbus, Ohio, hub, its founder, John Weikle, started raising capital to start the airline in that city. Two years later, the Skybus board hired Bill Diffenderffer as its CEO. Diffenderffer's prior airline experience was as in-house counsel for Eastern Airlines and CEO of Continental Airlines System One Reservations. At the time Skybus began operations it was the most heavily capitalized (funded) airline in US history. Its founder, John Weikle, resigned one day after Skybus began its first passenger flights.

On April 24, 2007, Skybus Airlines announced their initial set of eight destinations, all of which originated from their hub at Port Columbus International Airport in Columbus. At first, Skybus operated a strict point-to-point service, not booking flights between destination cities that were not Columbus, but the company later announced it would begin flying direct flights from its Portsmouth, NH, destination to two locations in Florida. In addition, prices of tickets and details on extra fees were announced the same day. Service between Port Columbus and the other eight destinations began on May 22, and the airline also announced its intention to expand rapidly. The expansion plans were not envisioned in the original business plan, and, in some instances, it expanded to cities that management did not choose on the basis of computer models used with its initial destination cities (Chattanooga, TN, for example). As part of its business model, Skybus favored smaller, cheaper airports near major markets. To serve Boston, for example, Skybus chose Portsmouth (New Hampshire) International Airport. Skybus marketed itself as an ultra-low-cost carrier, selling ten seats on each flight for $10. The low fares came with a reduction of frills. There were charges for virtually everything else (see Skybus business model), including checked baggage charges, which were later implemented by other carriers such as Delta, Northwest and United.

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