Five-axis milling is widely used to machine sculptured surface. To make good use of five-axis milling, effective tool path planning, whose key role is to determine optimized cutter posture, is critical. Existing literatures mainly focus on cutter posture optimization to avoid interference, and the effect of cutter posture on machining-induced residual stress is not reported. As residual stress greatly affects workpiece’s fatigue life and static strength, it is necessary to optimize residual stress. To fill up the gap, slotting with ball-end cutter on aluminum alloy blocks under different cutter posture is firstly carried out. Then, machining-induced residual stress is measured by X-ray stress instrument for each slot. Subsequently, machining-induced residual stress prediction model is developed using response surface methodology (RSM). Thirdly, cutter posture optimization method is proposed to minimize machining-induced residual stress. Finally, the proposed residual stress prediction and cutter posture optimization method are validated by various experiments.