The northern portion of State Road 43 begins at I–65 near Battle Ground in Tippecanoe County.

Going north, it passes through Brookston and Chalmers before terminating at US 24 and US 421 in Reynolds in White County.

The early 1950s renumbering of Indiana highways caused SR 43 to be concurrent.

SR 43 was concurrent with US 421 until the northern terminus was truncated to Reynolds in 1955 in favor of US 421.

A large portion of SR 43 from Lafayette to Spencer was eliminated in 1981 in favor of US 231.