The highway runs between its western terminus at SR 93 in West Lafayette and its eastern terminus at a diamond interchange with I-77 on the outskirts of the village of Stone Creek.

SR 751 traverses portions of Coshocton and Tuscarawas Counties.

[3] The designation of SR 751 came in 1962 along what was formerly designated SR 75 between the current western terminus in West Lafayette and the intersection with Bridge Street (formerly U.S. Route 21) in Stone Creek.

[4][5] The next year, the route between what is now County Road 9 in Oxford Township and Stone Creek became SR 75 and the final portion between West Lafayette and CR 9 became SR 75 by 1931.

[9][10] With the completion of I-77 around Stone Creek by 1971, and corresponding removal of US 21 from Ohio in that year, SR 751 was extended through Stone Creek from its previous eastern terminus along Bridge Street, then easterly from the split of Tuscarawas County Road 21 (former US 21) to its current eastern terminus at I-77's exit 73.