In the beginning of 2005, the airline drastically reduced flights at its Indianapolis hub to only three destinations and centered scheduled flights at Chicago Midway International Airport in order to complement Southwest Airlines codeshare flights. ATA also focused on serving markets that are business oriented and do not have Southwest service, such as San Francisco, Dallas/Fort Worth, and New York–LaGuardia. Additionally, ATA began offering point-to-point service not connecting to its Midway Hub, as to benefit other Southwest Airlines focus cities, such as Las Vegas, Orlando, and Phoenix, with connections to non-Southwest destinations such as Denver and Hawaii. Southwest CEO, Gary Kelly, said that revenues were up nearly 20% due to the new codesharing agreement. 

On March 28, 2005, ATA shut down its commuter airline service, Chicago Express/ATA Connection, and later sold the assets to a private buyer. In attempt to reduce operating costs, the airline also downsized its fleet by returning twenty Boeing 737-800 and eight Boeing 757-300 aircraft, along with numerous Boeing 757-200 aircraft. The eight 757-300 airframes were subsequently refurbished by Boeing, the lessor, and then leased to Continental Airlines. 

In mid-2005, ATA entered an agreement to lease three ex-United Airlines Boeing 737-300 aircraft. Three 737-300s entered service with ATA in late November 2005. Due to high lease rates, the three 737-300s were taken out of service in November 2007, and returned to their owners. In September 2005, ATA outsourced all its Heavy Maintenance Checks to overseas and domestic contractors. Also planned was an agreement with Continental Airlines to trade ATA's remaining four 757-300 aircraft for four 737-700 aircraft. In early October 2005, ATA terminated these negotiations due to the Boeing machinists strike, which would delay the delivery of the aircraft. 

On October 13, 2005, ATA announced major service reductions, ending flights to Boston, Minneapolis/St. Paul, and Newark. In addition, the planned addition of flights to Miami and Sarasota, Florida was cancelled. This ended Southwest codeshare service to Minneapolis and Newark. Later that year, on November 1, 2005, a second round of flight cuts were announced, including the suspension of scheduled service to Denver, San Juan, and their headquarters and former hub Indianapolis. 

On November 17, 2005, ATA Airlines received court approval to sell its Ambassadair Travel Club division to Grueninger Cruises and Tours. In a third round of cuts announced on December 6, 2005, ATA announced that it would discontinue service to three additional cities. ATA would suspend flights from Chicago Midway International Airport to San Francisco, Orlando, and Fort Myers in late April 2006. Following these cancellations, ATA would have only 18 daily scheduled departures from its former Chicago hub and 52 scheduled departures company-wide. Moreover, the company would be left with only 1 gate at Midway, down from its previous total of 14, surrendering the balance to Southwest or the city.