Ohio State Route 121 is a State Route in Western Ohio. It connects the cities of Versailles and Greenville to Richmond, Indiana. It is a north–south route for most of its existence, except the southern portion between Indiana and New Paris. It runs northeast-southwest through northern Preble County and Darke County with many curves and interesting changes in topography the further south you go. The northern terminus of the road is in downtown Versailles with State Routes 47 and 185. Route 121 is concurrent with 185 until the south end of Versailles. State Route 121 then goes southwest into Greenville. It is concurrent with State Routes 49 and 571 through parts of Greenville. Then 121 goes south through the towns of New Madison and New Paris. Route 121 makes a western turn in New Paris at its junction with State Route 320. It continues about 1-mile (1.6 km) until it reaches the Indiana border and becomes Indiana State Road 121. Indiana Route 121 continues on to meet us with U.S. Route 27 and Indiana State Road 227 in the north part of Richmond.

Ohio 121 is unusual in that it keeps its number after leaving Ohio. Ohio 49 and 527 are among the other Ohio state highways that do so, going north into Michigan and south into West Virginia respectively.