[4] One mile (1.6 km) later, the concurrency ends with SR 4 continuing to move north.

There are no more major intersections until SR 161 reaches Plain City, where it meets U.S. Route 42 (US 42).

[6] SR 161 goes through Madison and a small section of Franklin County without major intersections.

[8] Three miles (4.8 km) later, in Minerva Park, SR 161 becomes a limited access freeway.

One mile (1.6 km) later, SR 161 re-enters Columbus and meets I-270 again in a modified cloverleaf interchange.

Its east end was a junction with SR 21, five miles (8.0 km) west of Dublin.

[2] It was later expanded to include an unnumbered section between Mutual and Plain City, and Dublin and Granville.

[12] In 1938, a concurrency from five miles (8.0 km) west of Dublin to the city itself was changed from SR 31 to US 33.

SR 161's route was changed to use the bypass, no longer intersecting New Albany's downtown area.

[16] On June 14, 2004, Ohio Department of Transportation began the Northeast Expressway Transformation, replacing 17 bridges, 18 ramps, and 5 miles (8.0 km) of highway.

[22] An unsigned state route named SR 161J previously existed[23] in Licking County.