[2] U.S. Highway 61 closely parallels the route between La Crescent and Red Wing.

BNSF Railway operates a complementary St. Croix Subdivision which traces the eastern side of the river in Minnesota and Wisconsin.

The line was completed to Minnesota City in 1870, and made a junction with the Winona and St. Peter Railroad (under control of the Chicago and North Western Railway) in 1871.

The Milwaukee Road had a crossing in Winona and immediately made use of their new connection to Saint Paul.

Infrastructure for automatic cab signaling had been installed in the 1920s or 1930s, allowing the railroad to operate trains at high speed along the route with a good level of safety.