The highway runs from U.S. Route 61 (US 61) in Stanton, loops to the west around US 61 and the Natchez Trace Parkway to Fayette, and extends further north to Harriston.

Just north of this intersection, MS 553 makes a sharp curve to the east with a side road providing access to the Emerald Mound site.

The road crosses Coles Creek and again intersects the Natchez Trace Parkway, this time at a grade-separated one-quadrant interchange.

Continuing southeast, the road passes through wooded areas until it reaches the city limits of Fayette at its second intersection with US 61.

[2] MS 553 first appeared on state maps in 1956 however references to it was referenced in construction bids dating back to 1955.