Background <p>Dyslipidemia and elevated platelet count are independent risk factors for stroke, but their joint effect remains unclear. This study aimed to investigate the combined influence of dynamic lipid trajectories and platelet count on new-onset stroke risk in middle-aged and older Chinese adults.</p> Methods <p>A total of 7,917 stroke-free participants from the CHARLS cohort were enrolled and stratified into four lipid trajectory groups. Multivariable logistic regression, restricted cubic splines, interaction analysis, Cox proportional hazards model, and Fine–Gray competing risk model were used for analyses. All models were adjusted for medication use and other confounders. Additive interaction was evaluated using the relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (SI).</p> Results <p>During follow-up, 9.22% of participants developed stroke. Platelet count was linearly associated with new-onset stroke (per 10-SD increase: aOR = 1.019, <i>p</i> &lt; 0.001), and this association was significant only in the new-onset and persistent dyslipidemia groups. Significant multiplicative interaction was observed (<i>p</i> &lt; 0.001), but no significant additive interaction was found (all RERI 95% CI included 0). Results from Cox and Fine–Gray models were consistent with the main findings. Baseline balance between included and excluded participants was confirmed using standardized mean differences (SMD).</p> Conclusions <p>Elevated platelet count amplifies stroke risk in individuals with deteriorating or persistent dyslipidemia, showing a linear dose–response relationship. Integrated assessment of lipid dynamics and platelet count may help identify high-risk populations for precision stroke prevention.</p>