Initially, US 45 ran from Metropolis to Des Plaines, Illinois with some portions under construction. In 1929, a ferry that once crossed the Ohio River closed in favor of opening Brookport Bridge. By 1930, most of the sections were finished and then opened to traffic. The original alignment followed (from south–north) what used to be part of IL 1, IL 140, IL 25, IL 44, IL 51, and IL 46 before terminating at US 12. These state routes were eventually either truncated or removed as of 1935. That same year, US 45 was extended north from Des Plaines, Illinois to Michigan. In 1936, a new bridge crossing the Des Plaines River, Chicago Sanitary and Ship Canal, and the Illinois and Michigan Canal opened. As a result, US 45 moved off from another bridge carrying Willow Springs Road. In 1940, US 45 was rerouted to branch off west from Half Day instead of branching off north of Libertyville.