The Muzaffargarh district takes the name from the town where the headquarters is situated. Muzaffargarh literally means "Fort of Muzaffar", and is so called because the old town lies inside the walls of a fort built by Nawab Muzaffar Khan of Multan. Prior to that the place was known by a shop called Musan Hatti on the road leading from Multan to Dera Ghazi Khan. The district was originally called Khangarh, with the headquarters Khangarh. In 1859 the headquarters were moved to Muzaffargarh.
The area of the district is 6052 square miles (according to revenue record 1928 it is 5561 square miles). The population according to the census of 1921, is 568,478.