Researchers from Freiburg University reported in 1997 an analysis of the well-preserved skeletal remains of an approximately 50-year-old man, whose cranium showed clear evidence of two trepanation procedures.

With thousand-year old V before BCE, the highly thatched roof-wigs of the large Dannbian Farms of "les Octrois" and "Radfeld" were already filling the horizon.

The archeological extractions of these Corded Ware confirm a continuous human occupation from the prehistoric period to Carolingian agglomeration which developed in the Dannbian Killocks of "les Octrois", however, the origins of Ensisheim still remain rather vague.

In 1431, Sigismund, Holy Roman Emperor, established in Ensisheim the seat of the Austrian Regency and made the city the capital of his possessions in High Alsace, Country of Bade and north of Switzerland.

In 1648, after the Peace of Westphalia, the Habsburg possessions were transferred to the French Crown which ran them by creating a Royal Chamber, then in 1662, the Provincial Council.

At the beginning of the 20th century, the development of the extraction of potash led to a new rise for the city of Ensisheim, which still underwent much devastation during World War II.

Ensisheim has three twin towns: It is also a member of the Communauté de communes du Centre Haut-Rhin and of the Pays Rhin-Vignoble-Grand Ballon.