Designed to replace U.S. Route 51 (US 51) with an Interstate-grade freeway, the highway runs concurrently with US 20 in Rockford before joining I-90.

[5] Just north of the river, I-39 passes between the cities of LaSalle and Peru; as it intersects I-80 and US 6, it makes its southernmost connections with the Chicago region.

Approximately a mile east of the Alpine Road/US 20 interchange, I-39 joins US 20, moving from nearly entirely farmland to medium-density populated areas.

Bypassing Beloit to the east, it passes underneath the County Trunk Highway P bridge (CTH-P, Stateline Road).

After crossing the Rock River, I-39/I-90 has an interchange with WIS 59, connecting it with Edgerton (to the west) and Milton (to the southeast).

[7] Two miles (3.2 km) further north, the highway has an interchange with US 151 (splitting Madison and Sun Prairie); the northernmost Madison-area I-39 interchanges are US 51 (Madison and DeForest) and WIS 19 (Sun Prairie and Waunakee); CTH-V (West North Street) for DeForest serves as the last Dane County exit.

From Stevens Point northward, I-39 largely parallels the path of the Wisconsin River and Lake DuBay.

Following its entrance into Marathon County, WIS 153 connects to I-39 in Mosinee, adjacent to the Central Wisconsin Airport.

US 51, which ran mostly down the middle of the state, became a heavily traveled two-lane arterial road, experiencing many crashes and earning the nickname "Killer 51".

The Illinois Department of Transportation (IDOT) wanted the entire highway built to Interstate Highway standards, but a transportation committee established to review the proposed supplemental freeway system recommended only Interstate construction between Rockford and I-80.

[10] The highway from Oglesby south to Decatur was recommended to be an at-grade expressway, utilizing the existing road where possible.

After a decade of lobbying by interest groups, it was announced in 1986 that US 51 would be rebuilt to Interstate standards from Oglesby to Normal.

[18] In October 1993, the American Association of State Highway and Transportation Officials (AASHTO) established part of I-39 in its northern section between Rockford and Rib Mountain, Wisconsin, then designated I-39 along existing portions of I-90, I-94, and US 51.

However, this part of the highway was not marked as I-39 for another four years, primarily because the Wisconsin Department of Transportation (WisDOT) had to reconstruct the interchange connecting I-90 and I-94 with WIS 78 near Portage.

[20] The designation of I-39 violated Wisconsin's rule of not having any state trunk highway number duplicated—Interstate, US, or state—as WIS 39 already existed.