Existing optimization research on the crankshaft heat treatment process is mostly based on one-sided considerations, and less consideration is given to the matching of multiple process parameters, leading to irrational designs of heat treatment. To address this problem, this work investigates the influence mechanisms of cooling speed, tempering temperature, and holding time on the performance evaluation indexes of the straightness, residual stress, and martensite content of a crankshaft based on the response surface method. The results showed that the order of influence of these three different process parameters on the performance evaluation index was cooling speed > holding time > tempering temperature, and the order of influence on the performance evaluation indexes under multifactorial process parameters was cooling speed-holding time > cooling speed-tempering temperature > holding time-tempering temperature. The optimal process parameters were a cooling speed of 1.4 times the cooling oil, a tempering temperature of 555 °C, and a holding time of 6 h, with the straightness of the crankshaft reduced by 9.9%, the surface stress increased by 6.7%, and the martensitic content increased by 7.2% after the process optimization. This work can provide new clues for optimizing the heat treatment process parameters of crankshafts.