U.S. Route 51, mostly overlapped by the unsigned State Route 3 (SR 3), is a north–south state highway in the U.S. state of Tennessee, that is 135.9 miles (218.71 km) long. It begins in Shelby County and ends in Obion County. The SR 3 designation is seen largely on mileposts.

The two places where US 51 and SR 3 differ are in Memphis, where US 51 has been moved to Danny Thomas Boulevard (State Route 1 / State Route 4), while SR 3 remains on the one-way pair of 2nd and 3rd Streets, and in South Fulton, where US 51 crosses the state line on State Route 215 to the Purchase Parkway, while SR 3 remains on the old road, now U.S. Route 45.

US 51 enters Tennessee at Memphis and runs north through the cities of Millington, Covington, Henning, Ripley, Halls, Dyersburg, Troy, Union City, and South Fulton.

This highway crosses four interstate highways on its journey through the state and actually crosses Interstate 240 twice within the City of Memphis but interchanges with it only at Union Avenue. US 51 is the westernmost south–north United States Highway in the State of Tennessee. US 51 is an interstate standard facility from Dyersburg to South of Troy and then resuming interstate standard status north of Union City to South Fulton. US 51 is a four-lane or larger facility throughout the state with some sections north of Dyersburg carrying a 70 mph (110 km/h) speed limit.

Near Henning is also the site of the Hatchie River Bridge collapse on April 1, 1989 that killed 8 motorists when 3 spans of the structure collapsed. The 54-year old bridge was 45 miles (72 km) north of Memphis and carried the northbound lanes of US 51. Its collapse was the result of pier scour and movement of the river channel.

US 51 carries the Tennessee Scenic Parkway designation from its junction with SR 385 in Millington to SR 104 in Dyersburg and also carries the Great River Road designation from US 64/US 70/US 79 in Memphis to SR 88 in Halls.

US 51 traverses the counties shown in the table below.

Historic two-lane alignments of this highway from Henning north are represented by State Route 209, a portion of State Route 88, State Route 210, State Route 211, a portion of State Route 183 and State Route 184. From Memphis to Henning, most of the original two lane road was upgraded to four lane expressway in the 1960s.

Most of US 51 north of Dyersburg is expected to be upgraded as part of future Interstate 69. Plans currently call for Interstate 69 to run along the existing US 51 freeway from Dyersburg to Troy and from Union City to South Fulton. This section is part of SIU 7 for Interstate 69 and will require few changes beyond resigning the existing highway, however, a bypass route around Troy and Union City will need to be built before this section of future Interstate 69 is completed. See Interstate 69 in Tennessee for further information.