Due to the excellent properties of carbon fiber-reinforced polymers (CFRPs), such as high strength and strong corrosion resistance, the traditional water-jet-guided laser (WJGL) technology has problems with fiber pull-out and has a small cutting depth when processing CFRPs. Therefore, in this study, we used high-power water-jet-guided laser (HPWJGL) technology to perform groove processing experiments on CFRPs. The effects of four key process parameters, high laser power, pulse frequency, feed rate, and water-jet pressure, on the cutting depth were investigated by a single-factor experiment. The formation mechanism of groove cross-section morphology and the processing advantages of high-power water-jet-guided lasers were analyzed. On this basis, the mathematical prediction model of cutting depth was established by using the response surface method (RSM), and the optimal combination of process parameters was obtained. The mathematical prediction model was verified by experiments, and the error was only 1.84%, indicating that the model had a high reference value. This study provides a reference for the precision machining of HPWJGL technology.