U.S. Federal Route 50 runs briefly in the northwestern corner of Monroe County. The entire time this highway is in Monroe County, it is on Interstate 255. U.S. Rt. 50 passes through the following towns in Monroe County. Columbia U.S. Rt. 50 is multi-plexed in Monroe County. Interstate 255, from the St. Clair/Monroe County Line to Illinois/Missouri State Line.
SB I-255/WB U.S. Rt. 50 at the Mississippi River. SB I-255/WB U.S. Rt. 50 at the J.B. Bridge. SB I-255/WB U.S. Rt. 50 crossing the Mississippi River. NB I-255/EB U.S. Rt. 50 on the Illinois side of the JB Bridge. NB I-255/EB U.S. Rt. 50 at the Illinois Welcome Sign. (2006) NB I-255/EB U.S. Rt. 50 at the Illinois Welcome Sign. (September, 2007) A mileage sign on SB I-255/WB U.S. Rt. 50. A BGS on NB I-255/U.S. Rt. 50. A set of BGS's on NB IL St Rt 3. SB I-255/IL St Rt 3; WB U.S. Rt. 50 south of the Monroe/St. Clair County Line.