It has a length of 36.63 miles (58.95 km) and runs from west to east.

It has a western terminus at U.S. Highway 275 northwest of Wisner and an eastern terminus at the Burt County Missouri River Bridge at the Missouri River in Decatur.

It goes east into farmland and meets Nebraska Highway 9 west of Bancroft.

It continues east and skirts the southern edge of Bancroft, after which it meets Nebraska Highway 16.

After overlapping in Decatur, Highway 51 turns east and crosses the Missouri River via the Burt County Missouri River Bridge.