South Dakota Highway 45 is a state route that runs north to south across much of central South Dakota. The northern terminus is at the North Dakota border as a continuation of North Dakota Highway 3, and runs south to South Dakota Highway 44 at Platte. It is 198 miles (319 kilometers) in length.
By 1932, it was extended south along what was part of South Dakota Highway 47 to Wheeler. By 1936, SD 45 was truncated at Kimball (U.S. Highway 16), as U.S. Highway 281 supplanted the SD 45 designation to the south. In the early 1950's, when U.S. 281 was relocated several miles east, SD 45 was extended back south to SD 50.
The north end of the route has remained in its current configuration since 1936.