Frankenthal was first mentioned in 772. In 1119 an Augustinian monastery was built here, the ruins of which — known, after the founder, as the Erkenbertruine — still stand today in the town centre.
In the second half of the 16th century, people from the Netherlands, persecuted for their religious beliefs, settled in Frankenthal. They were industrious and artistic and brought economic prosperity to the town. Some of them were important carpet weavers, jewellers and artists whose Frankenthaler Malerschule ("Frankenthal school of painting") acquired some fame. In 1577 the settlement was raised to the status of a town by the Count Palatine Johann Casimir.
In 1600 Frankenthal was converted to a fortress. In 1621 it was besieged by the Spanish during the Thirty Years' War, and then successively occupied by troops of the opposing sides. Trade and industry were ruined and the town was not reconstructed until 1682.
However, in 1750, under the rule of the Elector (Kurfürst) Charles Theodore, Frankenthal was established as a centre of industry. Numerous factories were opened and mulberry trees were planted for silk production. In 1755 the famous Frankenthal porcelain factory was opened, which remained in production until 1800.
The beginning of modern industrialisation is dated from 1859.
In 1943 during a bombing raid the centre of the town was almost completely destroyed. In 1945, at the end of World War II, its industries in ruins, it was occupied first by the Americans and then by the French.
From 1946 Frankenthal has been part of the federal state of Rhineland-Palatinate. Today the town is again the site of some medium sized industries.