Background Delirium experienced poststroke is known to be associated with poor prognosis; however, the outcomes and functional consequences among patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis (intravenous tissue plasminogen activator) or intraarterial therapy are not well characterized. Methods Using data from 7 stroke centers with standardized delirium screening protocols, delirium was determined by a positive modified “Arousal, Attention, Abbreviated Mental‐Test, Acute Change Test” or Confusion Assessment Method for the Intensive Care Unit screen including diagnosis codes. Multivariable models were fit to estimate likelihoods of in‐hospital mortality, unfavorable discharge disposition, and longer length of stay among delirious patients with AIS, reported as adjusted odds ratios (aORs), adjusted incident rate ratios, and 95% CIs. A subset of patients with AIS with 90‐day modified Rankin scale (mRS) including those receiving intravenous tissue plasminogen activator or intraarterial therapy were analyzed for shifts in mRS scores associated with delirium, via ordinal logistic regression models. Results Between May 2016 and June 2021, AIS was the primary diagnosis in 12 409 hospitalization encounters representing 10 874 unique patients. Delirium was documented in 41.6% of AIS encounters, compared with 26.5% of age and mild cognitive impairment– or dementia‐matched non‐AIS encounters. Delirious (versus nondelirious) patients with AIS were older (median: 75 years versus 65 years), more frequently women (53.3% versus 48.7%), with a higher comorbidity burden (median Charlson Comorbidity Index: 7 versus 5). Delirious patients with AIS had higher odds of in‐hospital mortality (aOR, 2.66; [95% CI, 1.62–4.49]), unfavorable discharge disposition (aOR, 3.68; [95% CI, 3.15–4.30]), and longer length of stay (adjusted incidence rate ratio, 1.67; CI, 1.61–1.73). In the cohort of 2784 patients with treated and untreated AIS with 90‐day mRS, adjusted models indicated lower mRS (aOR, 0.54; CI, 0.46–0.63) associated with treatment, and higher mRS for delirious patients with AIS (aOR, 3.09; CI, 2.58–3.71). Among the subcohort of 948 patients with treated AIS, delirium remained significantly associated with higher mRS (aOR, 2.82; CI, 2.08–3.83). Conclusion Delirium is common among patients with AIS including those receiving intravenous tissue plasminogen activator or undergoing intraarterial therapy and prognosticates poor in‐hospital and 90‐day outcomes. Active screening and management of delirium may lead to improved stroke outcomes.