Contributions of measurements for detecting drowsy driving are determined by calculation parameters, which are directly related to the accuracy of drowsiness detection. The previous studies utilized the same Unified Calculation Parameters (UCPs) to compute each driver’s measurements. However, since each driver has unique driving behavior characteristics, namely, driver fingerprinting, Individual Drivers’ Best Calculation Parameters (IDBCPs) making measurements more discriminative for drowsiness are various. Regardless of the difference in driver fingerprinting among the drivers being tested, using UCPs instead of IDBCPs to compute measurements will limit the drowsiness-detection performance of the measurements and reduce drowsiness-detection accuracies at the individual driver level. Thus, this paper proposed a model to optimize calculation parameters of individual driver’s measurements and to extract individual driver’s measurements that effectively distinguish drowsy driving. Through real vehicle experiments, we collected naturalistic driving data and subjective drowsy levels evaluated by the Karolinska Sleepiness Scale. Eight nonintrusive drowsiness-related measurements were calculated by double-layer sliding time windows. In the proposed model, we firstly applied the Wilcoxon test to analyze differences between measurements of the awake state and drowsy state, and constructed the fitness function reflecting the relationship between the calculation parameters and measurement’s drowsiness-detection performance. Secondly, the genetic algorithms were used to optimize fitness functions to obtain measured IDBCPs. Finally, we selected measurements calculated by IDBCPs that can distinguish drowsy driving to constitute individual drivers’ optimal drowsiness-detection measurement set. To verify the advantages of IDBCPs, the measurements calculated by UCPs and IDBCPs were, respectively, used to build driver-specific drowsiness-detection models: DF_U and DF_I based on the Fisher discriminant algorithm. The mean drowsiness-detection accuracies of DF_U and DF_I were, respectively, 85.25% and 91.06%. It indicated that IDBCPs could enhance measurements’ drowsiness-detection performance and improve the drowsiness-detection accuracies. This paper contributed to the establishment of personalized drowsiness-detection models considering driver fingerprinting differences.