Background: The application of blood flow restriction (BFR) induces local ischemic hypoxia within the muscle(s) distal to the restriction device. Systemic hypoxemia via oxygen or barometric pressure manipulation achieves whole-body hypoxia and thus may be a more potent exercise adjunct than BFR. Therefore, the purpose of this study was to examine the acute effects of local ischemic hypoxia versus systemic hypoxemia on maximal voluntary isometric contraction (MVIC) torque, electromyographic amplitude (EMG AMP), EMG mean power frequency (MPF), and cognition. Materials and Methods: Twelve recreationally trained women (mean age ± standard deviation = 21 ± 1.6 years) performed 75 submaximal (1 × 30, 3 × 15) unilateral leg extension muscle actions under normoxia, local ischemic hypoxia, and systemic hypoxemia. Before and immediately after the 75 repetitions, MVIC muscle actions were performed, and surface EMG was simultaneously assessed from the vastus lateralis. Cognitive function was assessed immediately after each exercise using the Automated Neuropsychological Assessment Metrics (ANAM). Separate repeated-measures analyses of variance (ANOVAs) were performed to examine changes in MVIC, reaction time, EMG AMP, and EMG MPF responses during the MVIC muscle actions. Results: There were no significant (p = 0.21–0.953) Condition × Time interactions for MVIC, EMG AMP, or EMG MPF but a significant (p textless 0.001–0.005) main effect for the Time collapsed across Condition for MVIC torque (pretest 238.8 ± 19.5, posttest 212.7 ± 20.1 Nm) and EMG MPF (88.5% ± 1.4% of pretest). There were no significant (p = 0.503) differences in reaction time among Conditions. Conclusions: The findings of the present study suggest that all three conditions elicited comparable acute changes in performance as assessed by MVIC torque that were associated with no changes in muscle activation but decrease in action potential conduction velocity. Therefore, the application of local ischemic hypoxia or systemic hypoxemia during low-load resistance exercise can be used to elicit similar acute physiological responses and not adversely affect cognitive function relative to nonhypoxic conditions.