This study aimed to compare the acute biomechanical effects of three distinct sprint-specific priming strategies – resisted sprinting, assisted sprinting (i.e., overspeed), and technical wicket drills – on neuromechanical performance during 50-m sprint trials in elite youth sprinters. Twelve nationally ranked female youth sprinters (17.3 ± 0.8 years) participated in a randomized, repeated-measures protocol. Each athlete performed baseline 50-m maximal sprints, followed by three separate priming interventions, with performance re-evaluated at 24 h and 48 h post-activation. Key outcome measures included 50-m sprint time, reactive strength index (RSI), ground contact time (GCT), flight time (FT), step length, step frequency, duty factor, and asymmetry metrics. Data were analyzed using repeated-measures ANOVA, principal component analysis (PCA), k-means clustering, and machine learning classifiers. Assisted sprinting produced the greatest improvements in RSI (+0.13) and the largest reductions in GCT (−16 ms) at 48 h post-activation (p < 0.001). Resisted sprinting significantly increased step length (+0.09 m), while technical drills improved interlimb asymmetry and mediolateral control. PCA revealed two primary adaptation domains: PC1 (RSI, GCT, FT) and PC2 (interlimb asymmetry, mediolateral sway, and step frequency). Machine learning models (AUC = 0.83–0.85) identified the priming strategy, baseline asymmetry, and step frequency as the strongest predictors of ≥ 10% improvement in RSI. Sprint priming strategies elicited distinct neuromechanical responses that can be assessed during 50-m sprint trials. The overspeed protocol most effectively enhances force-time capacity and sprint performance, whereas technical drills primarily improve coordination. Integrating multivariate modeling facilitates the individualized prescription of priming protocols, offering a flexible and evidence-based approach to sprint optimization and athlete development.