This work demonstrates the use of Sobol’s sensitivity analysis framework to examine multivariate input–output relationships in dynamical systems. The methodology allows simultaneous exploration of the effect of changes in multiple inputs, and accommodates nonlinear interaction effects among parameters in a computationally affordable way. The concept is illustrated via computation of the sensitivities of atmospheric general circulation model (AGCM)-simulated tropical cyclones to changes in model initial conditions. Specifically, Sobol’s variance-based sensitivity analysis is used to examine the response of cyclone intensity, cloud radiative forcing, cloud content, and precipitation rate to changes in initial conditions in an idealized AGCM-simulated tropical cyclone (TC). Control factors of interest include the following: initial vortex size and intensity, environmental sea surface temperature, vertical lapse rate, and midlevel relative humidity. The sensitivity analysis demonstrates systematic increases in TC intensity with increasing sea surface temperature and atmospheric temperature lapse rates, consistent with many previous studies. However, there are nonlinear interactions among control factors that affect the response of the precipitation rate, cloud content, and radiative forcing. In addition, sensitivities to control factors differ significantly when the model is run at different resolution, and coarse-resolution simulations are unable to produce a realistic TC. The results demonstrate the effectiveness of a quantitative sensitivity analysis framework for the exploration of dynamic system responses to perturbations, and have implications for the generation of ensembles.