Drilling is one of very important machining processes in many applications of carbon fiber reinforced plastic (CFRP) composites. Rotary ultrasonic machining (RUM) has been successfully used in drilling of CFRP composites to overcome poor machinability. Cutting force is one of the most important output variables for evaluating drilling process, since it will greatly influence cutting temperature, tool wear, and surface conditions. Currently, there are no reported investigations on effect of input variables on cutting force using design of experiment (DOE) method in RUM of CFRP composites. Fivevariable two-level full factorial design has been conducted to study cutting force based on a mechanistic predictive model in RUM of CFRP composites. Main effects as well as interaction effects of five process variables (vibration amplitude, tool rotation speed, feedrate, abrasive size, and abrasive concentration) on cutting force are revealed.