Amphibians provide many ecosystem services valued by society. However, populations have declined globally with most declines linked to habitat change. Wetlands and surrounding terrestrial grasslands form habitat for amphibians in the North American Prairie Pothole Region (PPR). Wetland drainage and grassland conversion have destroyed or degraded much amphibian habitat in the PPR. However, conservation grasslands can provide alternate habitat. In the United States, the Conservation Reserve Program (CRP) is the largest program maintaining grasslands on agricultural lands. We used an ecosystem services model (InVEST) parameterized for the PPR to quantify amphibian habitat over a six-year period (2007–2012). We then quantified changes in availability of amphibian habitat under various land-cover scenarios representing incremental losses (10%, 25%, 50%, 75%, and 100%) of CRP grasslands from 2012 levels. The area of optimal amphibian habitat in the four PPR ecoregions modeled (i.e., Northern Glaciated Plains, Northwestern Glaciated Plains, Lake Agassiz Plain, Des Moines Lobe) declined by approximately 22%, from 3.8 million ha in 2007 to 2.9 million ha in 2012. These losses were driven by the conversion of CRP grasslands to croplands, primarily for corn and soybean production. Our modeling identified an additional 0.8 million ha (26%) of optimal amphibian habitat that would be lost if remaining CRP lands are returned to crop production. An economic climate favoring commodity production over conservation has resulted in substantial losses of amphibian habitat across the PPR that will likely continue into the future. Other regions of the world face similar challenges to maintaining amphibian habitats.