The highway begins at an intersection with US 10 and WIS-96 southeast of Fremont. It heads north from US 10 for about half a mile before turning westward. It passes through Fremont and heads to the northwest before turning to the south toward US 10 and WIS-49.
The highway then runs concurrently to the north with US 10 and WIS-49 for about 5 miles (8.0 km). It then splits off and heads northward into Weyauwega. After it leaves the city, the highway continues to the northwest, where it will meet with WIS-22 and WIS-54. It runs concurrently to the north along both highways before WIS-54 splits off. WIS-110 and WIS-54 continue concurrently northward, passing through Manawa. North of Manawa, the highways split and WIS-110 continues to the north. Further along, it enters Marion, where it terminates at US 45.
US 110 was deleted in 1939 and subsequently replaced with WIS 110. Due to a series of extensions and truncations in the 70 years since, however, WIS 110 is no longer designated on most of the former routing of US 110. Today, what was once US 110 is now US 45 from Oshkosh to Winchester, CTH-II from Winchester to US 10 southeast of Fremont, and WIS 110 from US 10 to WIS 96 east of Fremont.