The historic origin of the district is the Oberamt Karlsruhe. In 1809 it was split into one part responsible for the city Karlsruhe (Stadtamt), and one for the surrounding municipalities (Landamt). In 1865 however both parts were merged again to the Bezirksamt Karlsruhe. 1938 it was split again, this time with the district of Karlsruhe for the surrounding part, and the urban district of Karlsruhe for the urban area. In 1973 the district was enlarged by adding the complete district of Bruchsal and parts of the districts Sinsheim, Vaihingen, Pforzheim and Rastatt; some municipalities were also added to the city Karlsruhe and therefore left the district.
Since the founding of the Federal Republic, Karlsruhe has been the seat of the Federal Constitutional Court (Bundesverfassungsgericht), Germany's highest.
Starting in 1978 the district had a partnership with the Welsh county of Gwent. In 1996 Gwent was abolished, with the area split into several separate districts due to administrative reform, and the partnership has since continued with two new of these districts: Monmouthshire and Torfaen.
The top-left quarter of the coat of arms shows the symbol of Baden, which is appropriate since a large part of the Karlsruhe district belonged to Baden historically. The cross in the top-right is the symbol of the clerical state of Speyer. The three deer antlers in the bottom-right are the symbol of the state of Württemberg, and in the bottom-left is the symbol of the Wittelsbach family.