It runs from east to west for approximately 43 miles (69 km), serving only two counties: Madison and Hinds, while connecting the towns of Edwards, Flora, and Canton.

It heads north to immediately have an interchange with I-20/US 80 (Exit 19) before leaving Edwards and winding its way northeast as a two-lane highway through a mix of farmland and wooded areas for the next several miles.

The highway now crosses into Madison County and passes by the Mississippi Petrified Forest as it enters Flora along Peach Street to have an intersection with US 49.

MS 22 becomes W Peace Street as it widens to a four-lane undivided highway and travels through a business district, where it has an interchange with I-55/MS 16 (Exit 119).

The highway crosses a bridge over Bear Creek before narrowing to two-lanes at an intersection with W Fulton Street to pass through neighborhoods for several blocks before entering downtown.