The river Main forms a large horse-shoe bend in the district, entering in the southeast near Thüngersheim and leaving to the southwest near Hasloch. In the north it is joined by the Franconian Saale river at Gemünden. The Spessart hills cover most of the area of the district west and north of the Main. To the northeast, the district borders on the Rhön hills.
The district was established in 1972 by merging the former districts of Gemünden, Karlstadt, Lohr and Marktheidenfeld. Although Lohr is the largest town, the seat of the administration is located in Karlstadt.