As US 150 approaches Terre Haute, the route largely parallels US 41 east of the Wabash River as well as SR 63.

In the city of Terre Haute, as the pair approaches downtown, as well as the Vigo County Courthouse and the Indiana State University, the route then turns south along US 41 (3rd Street), a two-way, divided roadway.

As a concurrency, both US 41 and US 150 serve the CANDLES Holocaust Museum and Education Center, I-70/US 40, and the Terre Haute Action Track.

Near the Terre Haute campus of the Ivy Tech Community College, both routes meet SR 641 at a trumpet interchange.

After the road serves I-69 at a diamond interchange, the roadway downgrades to a two-lane undivided highway.

Between Loogootee and Shoals, the roadway parallels the East Fork White River.

In Prospect (located north of West Baden Springs and French Lick), SR 56 begins to run concurrently with US 150 all the way to Paoli.

After US 150 is alone once again, it then serves more towns: Chambersburg, Rego, Hardinsburg, Fredericksburg, Palmyra, Greenville, Galena, Mount St. Francis, and Floyds Knobs.

[4] Then, in October 1926, lots of state roads in Indiana were supplanted by their U.S. Route counterpart.