SH 351 begins at an intersection with US 83 Business (Treadaway Boulevard) in Abilene.

The highway heads east through Abilene along Ambler Avenue.

It curves to the northeast prior to a diamond interchange with Interstate 20 (I-20).

It continues to the northeast to its eastern terminus at a concurrency of US 180 and SH 6.

[2] SH 351 was commissioned in September 1943 to replace part of what had previously been designated US 80 Alternate (US 80 Alt.).