<b><i>Background:</i></b> Stroke risk scores (CHADS₂ and CHA₂DS₂-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. <b><i>Objective:</i></b> The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. <b><i>Methods:</i></b> We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS₂ and CHA₂DS₂-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. <b><i>Results:</i></b> A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA₂DS₂-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04–1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA₂DS₂-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA₂DS₂-VASc (aOR = 1.20, 95% CI = 1.04–1.38) and CHADS₂ scores (aOR = 1.24, 95% CI = 1.01–1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. <b><i>Conclusions:</i></b> High CHA₂DS₂-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.