Background: Preliminary evidence suggests that patients with atrial fibrillation (AF) detected after stroke (AFDAS) may have a lower prevalence of cardiovascular comorbidities and lower risk of stroke recurrence than AF known before stroke (KAF). Objective: We performed a systematic search and meta-analysis to compare the characteristics of AFDAS and KAF. Methods: We searched PubMed, Scopus, and EMBASE for articles reporting differences between AFDAS and KAF until June 30, 2021. We performed random- or fixed-effects meta-analyses to evaluate differences between AFDAS and KAF in demographic factors, vascular risk factors, prevalent vascular comorbidities, structural heart disease, stroke severity, insular cortex involvement, stroke recurrence, and death. Results: In 21 studies including 22,566 patients with ischemic stroke or transient ischemic attack, the prevalence of coronary artery disease, congestive heart failure, prior myocardial infarction, and a history of cerebrovascular events was significantly lower in AFDAS than KAF. Left atrial size was smaller, and left ventricular ejection fraction was higher in AFDAS than KAF. The risk of recurrent stroke was 26% lower in AFDAS than in KAF. There were no differences in age, sex, stroke severity, or death rates between AFDAS and KAF. There were not enough studies to report differences in insular cortex involvement between AF types. Conclusions: We found significant differences in the prevalence of vascular comorbidities, structural heart disease, and stroke recurrence rates between AFDAS and KAF, suggesting that they constitute different clinical entities within the AF spectrum. PROSPERO registration number is CRD42020202622