The independent territory was at first a county, the counts being descended from Henry I (Heinrich I.), youngest son of Simon I, count of Saarbrücken (d. 1182). This line, the Walramides, became extinct on the death of Count Eberhard (1393), who in 1385 had sold half his territory to the count palatine of the Rhine, and held the other half as his feudatory. Louis (d. 1489), son of Stephen, count palatine of Simmern-Veldenz, founded the line of the dukes of Zweibrücken. In 1559, a member of the line, Duke Wolfgang, founded the earliest grammar school of the town (Herzog-Wolfgang-Gymnasium), which existed until 1987. Duke Wolfgang also in 1557 converted his country to the new Lutheran faith.
After Charles X Gustav, the son of John Casimir, count palatine of Pfalz-Zweibrücken, succeeded his cousin Queen Christina of Sweden on the Swedish throne, Pfalz-Zweibrücken was in personal union with Sweden until 1718 though the House of Pfalz-Zweibrücken.
In 1731, the Zimmern-Veldenz line of the dukes of Zweibrücken became extinct and the duchy passed to the Birkenfeld branch, whence it came under the sway of Bavaria in 1799. At the Peace of Luneville in 1801 Zweibrücken was ceded to France; on its reunion with Germany in 1814 the greater part of the territory was given to Bavaria, the remainder to Oldenburg and Kingdom of Prussia. The city of Zweibrücken became part of the Palatine region of the Kingdom of Bavaria.
At the ducal printing office at Zweibrücken the fine edition of the classics known as the Bipontine Editions was published (1779 sqq.).
The last large social event before the First World War was the inauguration of the Rosengartens (rose gardens) by Princess Hildegard of Bavaria in June 1914. As consequence of the First World War, Zweibrücken was occupied by French troops between 1918 and 1930. In the course of Kristallnacht in 1938, the Zweibrücken synagogue were destroyed. With outbreak of the Second World War the city was evacuated in 1939-1940, as it lay in the ‘Red Zone’ on the fortified Westwall (Siegfried Line). Shortly before the end of the war, on 14 March 1945 the city was nearly completely destroyed from bombing by the Royal Canadian Air Force, with the loss of more than 200 lives. On 20 March American ground troops reached Zweibrücken. The city became part of the new state of Rhineland-Palatinate after the war.
In 1990 the city underwent a major change. With the departure of the Americans, the military area became free, which corresponded altogether to a third of the entire city surface. The unemployment ratio increased to approximately 21 %, leading to a decrease in demand in the retail trade of approximately 25 %. These events led to rapid, creative decisions on the part of the city, with the resultant changes becoming the model for other communities. Within the core of the city, a small pedestrian region was finished, which includes some restored historic buildings.
On the other side of the city was Kreuzberg Kasern, home to various units of the United States Army. Major tenants were the USA MATCOMEUR (Material Command, Europe, in 1973 the unit was renamed the US Army Material Management Agency, Europe.