It begins in Buxtehude and continues through Bergen, Celle, Hanover, Alfeld, Einbeck, Göttingen, Kassel, Marburg, Frankfurt, Darmstadt, Heidelberg, Karlsruhe and Freiburg in southwestern Germany and ends at Weil-Otterbach on the border with Switzerland.

In 1661 the Archbishop of Mainz and Hesse-Darmstadt agreed to divide the toll revenue: the Archbishophric controlled the road between Frankfurt and Heppenheim when the Frankfurt Fair took place, and Hesse-Darmstadt controlled the route at all other times.

Because of its importance to trade, in 1759 the portions immediately north and south of Heidelberg were turned into fixed roads.

In the early numbering system of 1932, the Reichsstraße 3 continued in what is today the stretch between Hamburg and Lübeck.

Although the stretch from Borken to Marburg is particularly irregular, it is frequently used by tractor trailers from the direction of Frankfurt that want to bypass the mountains and hills around Kassel.