Arkansas Highway 221 (AR 221 and Hwy. 221) is a designation for two north–south state highways in Carroll County, Arkansas.

Hwy. 221 begins at the Madison County, Arkansas−Carroll County line in northwestern Arkansas. The road continues south from here into the McIlroy Wildlife Management Area. The state highway travels in a northeast direction through the hills and forests southwest of Berryville before entering the Berryville city limits. In Berryville, it travels north and is known as Huntsville Street before turning onto West Carl Street and ending at US 62.

North of downtown Berryville, Hwy. 221 begins again at an intersection with Hwy. 21. It travels north to the Missouri state line where the highway continues as Missouri Highway 39 towards Springfield.