It begins north of Silerton at SR 100 and ends at the Tennessee–Mississippi state line, where it continues as Mississippi Highway 15.

It goes north as a 2-lane highway past several industrial businesses before entering Middleton and having an intersection with SR 57.

SR 125 then goes north past several more businesses before crossing the railroad tracks and passing through downtown.

The highway then leaves Middleton and continues north through rural areas for approximately 12 miles (19 km) before entering Bolivar.

For the next several miles, SR 125 winds its way through the countryside to Silerton, where it turns north and crosses into Chester County.