The monument for the 1862 Battle of Island Number Ten in the American Civil War is located on SR 22, about 3 mi (4.8 km) north of Tiptonville.

The highway passes through the park before turning north again to run alongside the Tennessee River, which it does so to its junction with U.S. Route 64 (US 64)/SR 69/SR 15 in Crump.

US 64/SR 15/SR 22 continue west, as a four-lane undivided highway, and cross back into McNairy County.

It continues north through mostly wooded areas before entering Lexington and widening to an undivided four-lane highway, just before meeting the northern terminus of SR 22A.

SR 22 continues north, passing through some neighborhoods before leaving Lexington and crossing the Big Sandy River to enter the countryside.

SR 22 then passes by a few businesses and a city park before leaving Parkers Crossroads and crossing into Carroll County.

SR 22 immediately becomes a divided highway and passes through a wooded area before entering Clarksburg and becoming undivided once again.

The highway goes through countryside again, passing by the Carroll County Airport, before entering McKenzie and having an intersection with SR 124.

They have an interchange with Industrial Park Drive before coming to the northern end of US 45E Business, where US 45E splits off to go north and SR 22 continues alone along the freeway.

SR 22 then merges on to become concurrent with US 51/SR 3 south, completely bypassing downtown to the north as a four-lane divided highway.

The SR 22 freeway section from Martin to Union City is proposed to be Interstate 169 (I-169), a 15 mile auxiliary route of I-69.

The highway travels due west for one block and curves to the northwest and enters Chester County.

Just on the outer city limits of Milledgeville, SR 22A curves to a western routing and enters Enville.

After a slight jog to the west, it resumes its north-northwesterly routing and leaves town.