Dating back to the early days of the state road system, SR 16 was first signed in the southern part of the state. It was moved to northern Indiana in 1926, running in two segments with the western segment being modern SR 14 from Illinois state line to Rochester and the eastern segment being modern US 224 in Indiana. During the 1930s, SR 16 was moved onto its modern routing from US 41 to SR 5. US 224 replaced SR 16 east of Huntington in the mid-1930s. The final section of SR 16 to be paved, the segment of roadway in Wabash County, was paved in the late 1960s.