U.S. Route 150 (US 150) in Indiana is a 176.315-mile-long (283.751 km) east–west highway that travels from the Illinois state line east of Paris, Illinois to Louisville, Kentucky at the Kentucky state line. A section of US 150 from New Goshen to Vincennes travels north–south instead of east–west. US 150 travels concurrently with its parent route, US 50, from Vincennes to Shoals. Between West Terre Haute and Terre Haute, US 150 travels along part of the historic National Road. Also, from Vincennes to New Albany, the route is designated as part of Indiana's Historic Pathways, as it roughly parallels what was then part of the Buffalo Trace.

U.S. Route 50 (US 50) is a part of the United States Numbered Highway System that runs from West Sacramento, California, to Ocean City, Maryland. In the U.S. state of Indiana, it is part of the state road system. US 50 enters the state in Vincennes. The 171.38 miles (275.81 km) of US 50 that lie within Indiana serve as a major conduit. All of the highway is listed on the National Highway System. Various sections are rural two-lane highway, urbanized four-lane undivided highway and one-way streets. The easternmost community along the highway is Lawrenceburg at the Ohio state line. US 50 passes through urban areas, farmland and woodland.