© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: In acute ischemic stroke, infarct location and volume have, separately, been used to determine long-term outcomes after stroke. Little information exists on the combination of these imaging characteristics on rehabilitation outcomes. We evaluated the association between infarct lesion location volume with the Functional Independence Measure (FIM) measure during inpatient rehabilitation facility (IRF) in ischemic stroke patients. Methods: Between 2012 and 2014, we prospectively enrolled consecutive acute ischemic stroke patients admitted from a Comprehensive Stroke Center and followed to an IRF in Chicago, Illinois. We adjudicated infarct volumes in specific lesion locations using a validated brain atlas. Volumes were calculated using an automated pipeline. FIM measure was extracted from IRF charts. We analyzed the association between acute infarct characteristics and functional measures using adjusted Spearman’s correlation. Results: Among 162 stroke patients (mean age 67.6 years, 48.1% male, 58.6% Caucasian), the median FIM at IRF was 52 (IQR 36–62). In an adjusted analysis, infarct volumes in the left basal ganglia (rs = − 0.45, p = 0.02) and left frontal lobe (rs = − 0.38, p = 0.04) were negatively correlated with FIM scores. Conclusions: There is an association between specific infarct lesion location volume and subsequent FIM scores assessed at IRF. Our findings suggest that imaging during index stroke hospitalization could be used to predict outcomes assessed during IRF.