N6-methyladenosine (m6A) modification is prevalent in the mammalian brain and functions as a significant epigenetic regulator in neurological disorders, including ischemic stroke. The fat mass and obesity-associated protein (FTO) was the first m6A demethylase to be identified. The objective of this study was to assess the prognostic significance of FTO in patients with acute ischemic stroke (AIS). A cohort consisting of 201 AIS patients and 53 healthy controls were enrolled, and their plasma FTO concentrations were measured. The findings demonstrated that FTO levels were remarkably lower in AIS patients compared to healthy controls (254.80 [229.89, 274.77] vs. 395.67 [271.34, 544.17], p < 0.001), and they were significantly diminished in patients with unfavorable outcomes compared to those with favorable outcomes (250.73 [208.34, 290.77] vs. 257.03 [236.47, 283.96], p = 0.016). Additionally, FTO concentration exhibited a negative correlation with 3-month modified Rankin scale (mRS) scores in ischemic stroke patients (r = - 0.1635, p = 0.0204). Univariate and multivariate logistic regression analyses revealed that plasma FTO levels were associated with the functional outcomes at 3 months. After adjusting for potential confounding variables, elevated FTO levels independently predicted the 3-month favorable outcomes (odds ratio [OR] = 0.986 (0.977-0.996), p = 0.004). Besides, the inclusion of FTO in the clinical model notably enhanced the discrimination and risk reclassification (integrated discrimination improvement = 5.34% (2.37-8.31%), p = 0.0004); continuous net reclassification improvement = 44.07% (17.33-70.82%), p = 0.0012). A nomogram incorporating FTO showed good calibration, discrimination, and clinical utility. Consequently, our study demonstrated that admission plasma FTO levels are independently linked to the 3-month outcomes for patients with AIS.