In order to improve the tribological properties of Ti-6Al-4V alloy and further broaden the application scope of titanium alloy materials in the industrial field, a preparation method of a waterjet-guided high-power laser processing surface microgroove was studied. In this paper, a multifocus coupling lens was innovatively designed to replace the spherical lens in the traditional waterjet-guided laser coupling device, which avoids the gas explosion phenomenon in the coupling of the high-power laser and waterjet, and realizes the high-quality coupling of the high-power laser and water beam fiber. Then, with the microgroove morphology as the response target, the single-factor test and response surface test of the water-guided laser processing microgroove were carried out. Based on the experimental results, an approximate mathematical model of the response surface between the process parameters and the microgroove topography target was constructed, and the quantitative relationship between the waterjet-guided laser processing parameters and the target response was studied. At the same time, the optimal combination of process parameters was obtained by multiobjective optimization, so as to effectively improve the microgroove morphology. This technology provides method guidance and a decision-making reference for subsequent waterjet-guided laser processing of titanium alloy surface functional microstructures.