It runs north–south in south central Wisconsin from the Illinois border near Gratiot to Portage.

The highway merges with US 12 and crosses the Wisconsin River, entering Sauk City before it turns to go north, now running concurrently with WIS 60.

A year later, this four-lane divided highway (and the WIS 78 designation with it) was extended northerly across the Wisconsin River then bypassing Portage to the west before merging into the existing two-lane route of US 51 north of the city.

The entire four-lane divided portion of WIS 78 from I-90/I-94 northerly to US 51 was shown as a full freeway with interchange beginning with the 1966 official state highway map, so it can be assumed the conversion to freeway occurred about this time (c.1965).

Then in 1996, US 51 from Rothschild (south of Wausau) southerly to Portage was concurrently designated as I-39 and to connect this new Interstate route with nearby I-90/I-94, the entire WIS 78 freeway from US 51 north of Portage to I-90/I-94 was redesignated as part of I-39, with WIS -78 losing approximately eight miles (13 km) of length in the process.