The route starts at MS 13 in the town of Lena, and it travels eastward across southern Leake County.

The road turns northeastward after halfway to its eastern terminus, and it ends at MS 487 near Tuscola.

MS 500 was designated in 1960 as a gravel road, and it was completely paved with asphalt eight years later.

The route leaves the corporate limit of Lena past Lyle Street and enters a forested area at Ealy Road.

It shifts westward slightly near Lindsey Road, and it crosses a stream that leads to a drainage ditch.