In this study, crumb rubber and diatomite were used to modify asphalt binder. Wet process was adopted as a preparation method, and the corresponding preparation process was determined firstly. The effects of six preparation parameters (crumb rubber concentration, diatomite concentration, shear time, shear speed, shear temperature, and storing time) on properties of modified asphalt binder (penetration at 25°C, softening point, ductility, viscosity at 135°C, elastic recovery, and penetration index) were investigated, and multiresponse optimization was conducted using the response surface method. The results revealed that softening points, viscosity, elastic recovery, and penetration index increase, while penetration and ductility decrease with the increase of crumb rubber concentration. Softening points, viscosity, and penetration index increase, while penetration and ductility decrease with the increase of diatomite concentration, which presents little influence on elastic recovery of binder. Shear temperature presented significant effects on penetration, softening point, viscosity, and ductility. Shear speed, shear time, and storing time have similar effects on binder properties because of their similar mechanism of action. Based on the model obtained from the response surface method, optimized preparation parameters corresponding to specific criteria can be determined, which possess favorable accuracy compared with experimental results.