Post-stroke seizures present a global challenge, yet its frequency and factors associated with its incidence are poorly documented, particularly in the Middle East. Thus, this study aims to investigate post-stroke seizure frequency and stroke-associated factors among ischemic stroke patients in Saudi Arabia, addressing demographic, clinical, and comorbid aspects to improve prognosis, diagnosis, prevention, and management. A multicenter, cohort observational study included eligible ischemic stroke patients who were categorized into those who developed seizures after injury and those who did not. Additionally, the study assessed the association between post-stroke seizure and 12-month mortality, 12-month stroke recurrence, and the occurrence of hemorrhagic transformation (HT) within 30 days. The study involved 1235 ischemic stroke patients, in which 13.5% developed post-stroke seizures. Patients with post-stroke seizures had more extended hospital stays, higher intensive care unit (ICU) admission rates, and a higher prevalence of comorbidities. Factors independently associated with post-stroke seizures included previous stroke history (OR = 1.93; 1.35–2.75), ICU admission (OR = 1.7; 1.15–2.5), and depression (OR = 2.1; 1.38–3.30). Logistic regression revealed associations between post-stroke seizures and HT (OR = 2.61; 1.70-4.00), stroke recurrence (OR = 2.30; 1.58–3.36), and mortality (OR = 1.89; 1.33–2.68). However, after adjusting for covariates, post-stroke seizures were significantly associated with stroke recurrence only (aOR = 1.7; 1.11–2.63). Our study identifies notable associations and risk factors for post-stroke seizures in ischemic stroke patients. This underscores the importance of adopting a comprehensive approach to stroke care to enhance the prediction, prevention, and management of post-stroke seizures. Further research is warranted to validate these findings, enhance the understanding of post-stroke seizure mechanisms, and guide management strategies.