South Dakota Highway 45 is a state highway that runs north to south across much of central South Dakota, United States. 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 km) in length.

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SD 45 was established around 1927. The southern terminus was at the intersection of present-day SD 50 and County Road 49 (CR 49) and the northern terminus was at the intersection of SD 10 in Leola.

By 1932, it was extended south along what was part of SD 47 to Wheeler. By 1936, SD 45 was truncated at Kimball, at US 16, as US 281 supplanted the SD 45 designation to the south. In the early 1950s, when US 281 was relocated several miles to the east, SD 45 was extended back south to SD 50.

Around 1970, SD 50 had been realigned to intersect SD 44 west of Platte, and SD 45 was extended south along the old alignment to Platte, where it remains today.

The north end of the route has remained in its current configuration since 1936.

This section is missing mileposts for junctions. Please help by adding them.

County	Location	mi	km	Destinations	Notes
Charles Mix	Platte			SD 44 / SD 50 – Winner	Southern terminus
Brule	​			I-90 east – Mitchell	Eastern end of I-90 concurrency, Exit 289.
	Kimball			I-90 west – Rapid City	Western end of I-90 concurrency, Exit 284.
Buffalo	​			SD 34 – Wessington Springs
Hand	Miller			US 14 east – St. Lawrence	Southern end of US 14 concurrency
				US 14 west – Pierre	Northern end of US 14 concurrency
	​			SD 26 east	Southern end of SD 26 concurrency
	​			SD 26 west	Northern end of SD 26 concurrency
Hand–Faulk county line	​			US 212 east – Redfield	Southern end of US 212 concurrency
Faulk	​			US 212 west – Faulkton	Northern end of US 212 concurrency
	​			SD 20 east – Northville	Southern end of SD 20 concurrency
	​			SD 20 west – Onaka	Northern end of SD 20 concurrency
Edmunds	Ipswich			US 12 west – Roscoe	Western end of US 12 concurrency
	​			US 12 east – Aberdeen	Eastern end of US 12 concurrency
McPherson	Leola			SD 10 east – Britton	Eastern end of SD 10 concurrency
	​			SD 239 north – Long Lake
	​			SD 10 west / SD 247 south	Northern terminus; western end of SD 10 concurrency
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus

• List of state highways in South Dakota

• South Dakota Highways Page: Highways 31-60