<p>Rhabdomyolysis is a potentially fatal adverse reaction mainly caused by certain medications. Few real-world studies have shown a clear association between atypical antipsychotics and rhabdomyolysis. This study aimed to evaluate the association between atypical antipsychotics and rhabdomyolysis using the FDA Adverse Event Report System (FAERS) database. The data were obtained from the FAERS database from January 1, 2004 to December 31, 2023. To identify potential risk signals from the FAERS database, a disproportionality analysis was conducted using the reporting odds ratio (ROR) and corresponding 95% confidence intervals (CIs) with <i>p</i>-values adjusted via Bonferroni correction. The time to onset, hospitalization rate, and mortality of atypical antipsychotics associated rhabdomyolysis were also investigated. A total of 2360 rhabdomyolysis case reports from the FAERS database were considered. Quetiapine had the greatest proportion (27.75%). Olanzapine had the highest positive signal values of rhabdomyolysis. Statistically significant rhabdomyolysis RORs (95% CI) for atypical antipsychotics were (in descending order): olanzapine 4.02 (3.72–4.35), quetiapine 3.81 (0.53–27.6), ziprasidone 2.76 (2.19–3.49), risperidone 2.12 (1.91–2.35), aripiprazole 2 (1.8–2.21), clozapine 1.47 (1.31–1.64). In the time to onset analysis, all atypical antipsychotics associated rhabdomyolysis had early failure type characteristics, the risk of rhabdomyolysis occurrence would be gradually decreased over time. Our study highlights the importance of vigilant patient monitoring following the prescription of atypical antipsychotics to reduce the risk of rhabdomyolysis. It is necessary to monitor serum creatinine kinase (CK) level early, especially during dose adjustment or initiation of new atypical antipsychotics. This research may provide a valuable information for patients, clinicians, and others concerned with the safety of atypical antipsychotics, and optimize clinical practice.</p>