Theoretical models of panic disorder posit a unique role for external anxiety-related control attributions (i.e., lack of perceived control over the onset and maintenance of one’s anxiety symptoms) in predicting panic reactivity, even beyond well-established cognitive risk factors such as anxiety sensitivity. The present study examined whether anxiety-related control attributions would uniquely predict a range of anxious responses across multiple phases and sessions of a biological stressor. Undergraduate students (N = 317) completed measures of anxiety-related control attributions and anxiety sensitivity prior to undergoing a 7.5 % carbon dioxide (CO2) challenge. A subset of these participants (N = 102) returned 1 week later for a second administration. Self-reported subjective distress, physical panic symptoms, and panic-related threat cognitions were measured at baseline and again during several phases of the challenge procedure. Physiological measures of heart rate, skin conductance, and respiration rate were also recorded throughout the challenge. Consistent with theoretical models, higher external control attributions uniquely predicted greater reactivity on all self-report indices across challenge phases and sessions; findings were more mixed for the physiological indices, with higher external control attributions predicting higher heart rate but lower skin conductance, and no prediction for respiration rate. Implications for theory and treatment of panic pathology are discussed.