Mathematics anxiety is a major impediment to achievement in mathematics and science academic domains. Although important steps have been made in understanding the psychological processes of mathematics anxiety, as well as developing promising interventions, less is known about the relationship among mathematics anxiety, affective and biological responses, and achievement in stressful performance contexts. Toward this end, the research presented here recruited community college students (N = 478) from 30 mathematics classrooms, and examined associations among mathematics anxiety, stress appraisals, neuroendocrine reactivity (cortisol and testosterone), and exam scores. Higher levels of mathematics anxiety associated with students perceiving more demand and fewer coping resources in exam settings, lower levels of testosterone on exam days relative to baseline, and worse exam performance. Moreover, associations among mathematics anxiety, and neuroendocrine reactivity and performance were partially mediated by stress appraisals. Implications for student achievement, wellbeing, and intervention development are discussed.