This study examined the impact of noise on cognitive performance in autism spectrum disorder (ASD), while concurrently measuring sympathetic responses. Adolescents with and without ASD completed visually presented span tasks in a 2 × 2 experimental manipulation of noise (quiet vs. 75 dB gated broadband noise) and task difficulty (easier vs. harder). Analyses revealed a significant noise × difficulty interaction on performance, and a significant group × noise × difficulty interaction on sympathetic arousal. Correlational analyses indicated an adaptive effect of noise and increased arousal on performance in the easier condition for the control group and a detrimental effect of noise and increased arousal in the harder condition for the ASD group. Implications for sensory processing research and intervention development are discussed.