Introduction: Whether the association between atrial fibrillation (AF) and ischemic stroke (IS) outcomes differs by IS treatment type is unknown. We hypothesize that patients with IS who have AF will have a worse NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) score than non-AF, with differences by IS treatment type. Methods: Patients with, and without AF admitted to Johns Hopkins (2020–2023) with confirmed IS and complete covariates were eligible for inclusion. Consecutive patients either received acute IS treatment (intravenous tissue plasminogen activator (IVtPA), mechanical thrombectomy (MT), or both) or did not receive treatment (2:1 ratio). Multivariable regression models were used to determine the association between AF and discharge NIHSS, or 90-day mRS, separately, with interaction terms for IS treatment type as appropriate. Results: Among 353 IS patients (mean age 69 years, 52.1% female, 54.7% Black), 62 received IVtPA only, 66 received IVtPA then MT, 108 received MT only, and 117 were not treated. Patients with AF (N = 152) were, on average, 11 years older and had more comorbidities than non-AF. AF was associated with higher odds of an NIHSS > 5, even after adjusting for demographics and comorbidities (OR 2.09, 95% CI 1.29–3.40). AF increased the odds of a worse 90-day mRS (Ordinal OR 1.65, 95% CI 1.03–2.64). The association between AF and NIHSS differed by whether MT was received (p-interaction 0.037), but not by IVtPA (p-interaction 0.105). AF and 90-day mRS differed by whether MT was received (p-interaction 0.020), but not by IVtPA (p-interaction 0.139). Patients with AF who did not receive MT had a worse NIHSS (OR 4.24, 95% CI 1.38–13.00) and 90-day mRS (OR 2.79, 95% CI 1.30–1.97) compared to non-AF. The individual effect estimates were not significant for those treated with MT when comparing AF to non-AF. Conclusions: The association between AF (vs non-AF) and both NIHSS and 90-day mRS differed by whether MT was received, but not by IVtPA. Patients with AF who did not receive MT had more severe strokes and worse outcomes than non-AF. These findings suggest that while AF is typically linked to more severe strokes, not receiving MT when eligible is particularly detrimental. Receipt of IVtPA did not appear to make a difference, possibly due to treatment contraindications and delays among those with AF.