The route was fully paved by the end of the 1930s and served as a part of US 72 until 1986, when a new divided highway was built to the south.

[3] Several miles later, the route turns more east and the surroundings become more developed as it becomes Quitman Street and reaches an intersection with MS 25 on the western edge of Iuka.

[3] MS 172 leaves Iuka and heads back into forests as an unnamed road, running a short distance to the southwest of Norfolk Southern's Memphis District — West End railroad line.

MS 172 makes a sharp turn south away from the railroad tracks and comes to its eastern terminus at US 72 immediately west of the Alabama border near Oldham.

[4] What is now MS 172 was originally designated as a part of the Lee Highway, an auto trail that connected Washington, D.C. with San Diego, in 1920.