It was bounded by (from the north and clockwise) the districts Delitzsch, Torgau-Oschatz, Döbeln, Mittweida and Leipziger Land.

In 1952 the area around Wurzen was split off from the district Grimma.

This was reverted in 1994 when the two previous districts Grimma and Wurzen were merged again.

A few municipalities from other districts around Bad Lausick were added as well.

The district is named after its major river, the Mulde – the name Muldental means valley of the Mulde.