It rises as the White Main in the Fichtel Mountains of northeastern Bavaria[a] and flows west through central Germany for 525 kilometres (326 mi) to meet the Rhine below Rüsselsheim, Hesse.

The Red Main originates in the Franconian Jura mountain range, 50 km (31 mi) in length, and runs through Creussen and Bayreuth.

Because the river is rather narrow on many of the upper reaches, navigation with larger vessels and push convoys requires great skill.

The Main also passes the following towns: Burgkunstadt, Lichtenfels, Bad Staffelstein, Eltmann, Haßfurt, Schweinfurt, Volkach, Kitzingen, Marktbreit, Ochsenfurt, Karlstadt, Gemünden, Lohr, Marktheidenfeld, Wertheim, Miltenberg, Obernburg, Erlenbach/Main, Aschaffenburg, Seligenstadt, Hainburg, Hanau, Hattersheim, Flörsheim, and Rüsselsheim.

[5] In a historical and political sense, the Main line is referred to as the northern border of Southern Germany, with its predominantly Catholic population.

Approximately 600 kilometres long (370 mi), it is the first long-distance instance awarded 5 stars by the General German Bicycle Club (ADFC) in 2008.