The Milwaukee–Beloit route was chosen, completed in 1976 as WIS 15 and renumbered as I-43 in 1988. The Beloit-to-Milwaukee segment was developed after two separate proposals for Interstates, one of them between Milwaukee and Beloit and the other between Milwaukee and Janesville. Controversy about this location and use of right-of-way led to the establishment of the current alignment, which follows much of what was the 1950s-era realignment of US 141 from Milwaukee to Sheboygan, and a new alignment from Sheboygan to Green Bay. The route was originally planned to follow an alignment about midway between US 41 and US 141 (the latter paralleled Lake Michigan at the time) along WIS 57. Only the Milwaukee-to-Green Bay section was approved. I-43 came about as a result of toll road proposals that included a Milwaukee to Superior corridor that included Hurley, Wausau, and Green Bay.

There are no auxiliary or business routes connected to I-43, though an alternate route to direct traffic during road closures is signed along local and state highways from Milwaukee County north into Brown County. State Trunk Highway 32 (WIS 32) runs concurrently with I-43 in two sections and I-94, I-894, US 10, US 41, US 45, WIS 57, and WIS 42 overlap I-43 once each. Highway 41 (US 41) and US 141 in Green Bay. Interstate 43 ( I-43) is a 191.55-mile-long (308.27 km) Interstate Highway located entirely within the US state of Wisconsin, connecting I-39/ I-90 in Beloit with Milwaukee and I-41, U.S. Rock, Walworth, Waukesha, Milwaukee, Ozaukee, Sheboygan, Manitowoc, Brown

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