Climate change is a major challenge for managers of protected areas world-wide, and managers need information about future climate conditions within protected areas. Prior studies of climate change effects in protected areas have largely focused on average climatic conditions. However, extreme weather may have stronger effects on wildlife populations and habitats than changes in averages. Our goal was to quantify future changes in the frequency of extreme heat, drought, and false springs, during the avian breeding season, in 415 National Wildlife Refuges in the conterminous United States. We analyzed spatially detailed data on extreme weather frequencies during the historical period (1950–2005) and under different scenarios of future climate change by mid- and late-21st century. We found that all wildlife refuges will likely experience substantial changes in the frequencies of extreme weather, but the types of projected changes differed among refuges. Extreme heat is projected to increase dramatically in all wildlife refuges, whereas changes in droughts and false springs are projected to increase or decrease on a regional basis. Half of all wildlife refuges are projected to see increases in frequency (> 20% higher than the current rate) in at least two types of weather extremes by mid-century. Wildlife refuges in the Southwest and Pacific Southwest are projected to exhibit the fastest rates of change, and may deserve extra attention. Climate change adaptation strategies in protected areas, such as the U.S. wildlife refuges, may need to seriously consider future changes in extreme weather, including the considerable spatial variation of these changes.