This paper uses freight performance measure (FPM) data to assess quantitatively the local effects of an Interstate closure. The use of FPM data allows for an empirical analysis beyond traditional theoretical modeling, simulations, user surveys, windshield surveys, and manual traffic counts. Specifically, this paper presents a case study of the localized changes in regional freight flows with origins and destinations in Kansas City, Missouri, and Kansas City, Kansas, and in Omaha, Nebraska, and Council Bluffs, Iowa, during the Missouri River flooding of 2011, which caused 49 mi of Interstate 29 to be closed for 115 days. Analysis results show that most of the regional truck traffic did not adhere to the detour routes designated by the state department of transportation, which aimed to keep the trucks on Interstates or four-lane divided facilities. Other routes used were found to be advantageous for driver costs, vehicle operating costs, travel time, and vehicle miles traveled. On average, as a result of the closure, vehicle and driver costs increased by an estimated 10.1%, travel time increased by 21%, and vehicle miles traveled increased by 12%. Finally, analysis of the progression of route selection during the 4-month period of the Interstate closure concluded that regional truck route selection progressed during the 4 months to the most efficient alternate routes between Kansas City and Omaha–Council Bluffs.