Background: Neurological manifestations of coronavirus disease 2019 (COVID-19) have been highlighted. COVID-19 potentially increases the risk of thromboembolism. We aimed to compare patients with COVID-19 with and without new-onset acute ischemic stroke (AIS). Materials and Methods: In this single-center retrospective case–control study, demographics, clinical characteristics, laboratory findings, and clinical outcomes were compared between 51 patients with both COVID-19 and AIS (group A) and 160 patients with COVID-19 and without AIS (group B). Results: Patients in group A were significantly older, more likely to present with critical COVID-19 (P = 0.004), had higher rates of admission in the intensive care unit (P < 0.001), more duration of hospitalization (P < 0.001), and higher in-hospital mortality (P < 0.001). At the time of hospitalization, O₂ saturation (P = 0.011), PH (P = 0.04), and HCO3 (P = 0.005) were lower in group A. White blood cell count (P = 0.002), neutrophil count (P < 0.001), neutrophil-lymphocyte ratio (P = 0.001), D-Dimer (P < 0.001), blood urea nitrogen (BUN) (P < 0.001), and BUN/Cr ratio (P < 0.001) were significantly higher in patients with AIS. Conclusion: Stroke in COVID-19 is multifactorial. In addition to conventional risk factors of ischemic stroke (age and cardiovascular risk factors), we found that patients with more severe COVID-19 are more prone to ischemic stroke. Furthermore, leukocyte count, neutrophil count, neutrophil-lymphocyte ratio, D-Dimer, BUN, and BUN/Cr ratio were higher in patients with AIS following COVID-19 infection.