Recent studies have demonstrated that multiple co-occurring global changes can alter the abundance, diversity, and productivity of plant communities. Belowground processes, often mediated by soil microorganisms, are central to the response of these communities to global change. Very little is known, however, about the effects of multiple global changes on microbial communities. We examined the response of ammonia-oxidizing bacteria (AOB), microorganisms that mediate the transformation of ammonium into nitrite, to simultaneous increases in atmospheric CO2, precipitation, temperature, and nitrogen deposition, manipulated on the ecosystem level in a California grassland. Both the community structure and abundance of AOB responded to these simulated global changes. Increased nitrogen deposition significantly altered the structure of the ammonia-oxidizing community, consistently shifting the community toward dominance by bacteria most closely related to Nitrosospira sp. 2. This shift was most pronounced when temperature and precipitation were not increased. Total abundance of AOB significantly decreased in response to increased atmospheric CO2. This decrease was most pronounced when precipitation was also increased. Shifts in community composition were associated with increases in nitrification, but changes in abundance were not. These results demonstrate that microbial communities can be consistently altered by global changes and that these changes can have implications for ecosystem function.