Isoprenoids (isoprene and monoterpenes) are the most dominant class of biogenic volatile organic compounds (BVOCs) and have been shown to significantly affect global tropospheric chemistry and composition, climate, and the global carbon cycle. In this study we assess the sensitivity of biogenic isoprene and monoterpene emissions to combined and isolated fluctuations in observed global climate and atmospheric carbon dioxide (CO2) concentration during the period 1971–1990. We integrate surface emission algorithms within the framework of a dynamic global ecosystem model, the Integrated Biospheric Simulator (IBIS), to simulate biogenic fluxes of isoprenoids as a component of the climate-vegetation dynamics. IBIS predicts global land surface isoprene emissions of 454 Tg C and monoterpenes of 72 Tg C annually and captures the spatial and temporal patterns well. The combined fluctuations in climate and atmospheric CO2 during 1971–1990 caused significant interannual and seasonal variability in global biogenic isoprenoid fluxes that was somewhat related to the El Niño-Southern Oscillation. Furthermore, an increasing trend in the simulated emissions was seen during this period that is attributed partly to the warming trend and partly to CO2 fertilization effect. The isolated effect of increasing CO2 during this period was to steadily increase emissions as a result of increases in foliar biomass. These fluctuations in biogenic emissions could have significant impacts on regional and global atmospheric chemistry and the global carbon budget.