Its western terminus is at exit 237 of Interstate 70 (I-70) in Berkeley near Lambert-St. Louis International Airport.

Route 115's eastern terminus is also at I-70, at exit 248A, in St. Louis, near the McKinley Bridge.

It is one of two Missouri Highways that has an odd-numbered designation, yet runs in an east–west direction.

Prior to the construction of I-70 and several phases of expansion of Lambert Airport, Route 115 continued west as far as St. Charles, which included a portion of Natural Bridge Road in Bridgeton which has been significantly impacted by recent airport expansion.

Portions of the same right-of-way exist as a section of St. Charles Rock Road (which is now Route 180) west of I-270.