Highway 41 also extends through Kentucky. Entering the Commonwealth just south of Evansville, it extends southward through Henderson, Madisonville, and Hopkinsville. In Kentucky, it is paralleled by the Pennyrile Parkway. There is also an Alternate 41 in Kentucky. The bridge across the Ohio River is often struck by barges forcing many closings of the highway. The highway also passes through Tennessee, Georgia, and Florida.
Highway 41 was once the major route from the Midsouth to Florida; however, the rise of the Interstate Highway has diminished this role. Eventually, the stretch between Evansville, Indiana and Henderson, Kentucky will be superseded by Interstate 69.