During the 12th and 13th century, the history of the entire province of Berry, including the Lordship of Issoudun, was marked by the Capetian–Plantagenet rivalry. In 1195, Richard I of England defended the city from the advances of Philip II of France. Two kings met in December 1195 between Issoudun and Chârost, and reached an agreement, known as the Treaty of Issoudun. Around this time the beak-shaped keep of the castle was built. By the Treaty of Le Goulet (1200), Lords of Issoudun (French: Seigneurs d'Issoudun) returned to the suzerainty of the French Crown. The most prominent Lords of Issoudun from that period were Odo III and his son Raoul III, who was married to Margaret of Courtenay. Since Raoul III of Issoudun died (c. 1213) without direct male heirs, the Lordship was passed to several secondary heirs, through the female line of succession. First of them was William I of Chauvigny (French: Guillaume I de Chauvigny) in 1217, but final settlement was reached in 1221, after the intervention of the French Crown.
In 1917, the U.S. Air Service established its largest European training centre, the 3rd Aviation Instruction Center, about nine miles northwest of the town. At the time of the Armistice, 11 November 1918, thirteen fields were in operation and well over 10,000 ground personnel, student pilots and instructors were located there. It was at that time the largest air base in the world. A single monument on Department Route 960 remains to mark Issoudun's part in the Great War.
The United States Air Service formally left Issoudun on 28 June 1919, almost eight months after the war ended. The sites of the former airfields have returned to their previous status as agricultural fields.
On 28 June 2009, the people of Issoudun had a commemoration ceremony in honour of the American aviators who had trained, and in many cases, died while training there.
The International broadcasting center of TDF (Télédiffusion de France) is at Issoudun/Ste Aoustrille. Issoudun is currently used by TDF for shortwave transmissions. The site uses 12 rotary ALLISS antennas fed by 12 transmitters of 500 kW each to transmit shortwave broadcasts by Radio France International (RFI), along with other broadcast services.