It splits off from U.S. Route 45 near Metropolis (across the Ohio River from Paducah, Kentucky) and runs north, rejoining U.S. 45 in Harrisburg.

It is multi-plexed with Illinois 34 from its northern terminus at U.S. 45 in Harrisburg through Pankeyville and on to Mitchellsville where 34 spurs east to Rosiclaire.

The route also meets Illinois 147 6 miles south of Eddyville just north of Glendale.

In fact it saves several miles from having to drive south to 146 at Dixon Springs and then east on to Golconda.

SBI Route 145 originally ran from Metropolis north to Dixon Springs.