Climate change has the potential to be a source of increased variability if crops are more frequently exposed to damaging weather conditions. Yield variability could respond to a shift in the frequency of extreme events to which crops are susceptible, or if weather becomes more variable. Here we focus on the United States, which produces about 40% of the world’s maize, much of it in areas that are expected to see increased interannual variability in temperature. We combine a statistical crop model based on historical climate and yield data for 1950–2005 with temperature and precipitation projections from 15 different global circulation models. Holding current growing area constant, aggregate yields are projected to decrease by an average of 18% by 2030–2050 relative to 1980–2000 while the coefficient of variation of yield increases by an average of 47%. Projections from 13 out of 15 climate models result in an aggregate increase in national yield coefficient of variation, indicating that maize yields are likely to become more volatile in this key growing region without effective adaptation responses. Rising CO2 could partially dampen this increase in variability through improved water use efficiency in dry years, but we expect any interactions between CO2 and temperature or precipitation to have little effect on mean yield changes.