Domžale was attested in written sources circa 1200–1230 as Domsselsdorf (and as Vnheilden dorf in 1260, Vnsselsdorf in 1302, Vnsersdorf in 1322, Dumsel in 1490, and Damschale in 1558, among other variations.)

The medieval German name Unser(s)dorf is derived from (D)unselsdorf, which was presumably borrowed from the Slovene name and from which the initial D- was lost because it was reanalyzed as a definite article.

The Slovene name could be reconstructed as *Domžaľe, based on a Slavic personal name such as *Domožalъ and referring to an early inhabitant of the place.

Alternatively, the Slovene name may be borrowed from Middle High German Domsell(sdorf), based in turn on a Slavic name such as *Domoslavъ.

After Slovenia declared independence, on 27 June 1991 the Yugoslav army attacked barricades in the town, and bombed the radio transmitter and houses.