SR-16 begins at the Wyoming state line south of Woodruff, as an extension of WYO 89, and heads northwest ten miles (16 km) to Woodruff, where it turns north through the town center.

[1] SR-16 then continues north ten miles (16 km) to Randolph, running through the town center.

North of Randolph, it runs generally north-northeast nine miles (14 km) to end at an intersection with SR-30 at Sage Creek Junction.

A 1921 law added the portion of the road from Evanston, Wyoming to Montpelier, Idaho in Utah to the state highway system, as well as the branch towards Kemmerer, Wyoming.

[2] The State Road Commission assigned the State Route 3 designation to the highway that decade,[3] and in 1927 the legislature officially adopted the number for the main route and the spur.