Oil and natural gas have been produced in Wyoming since the late 1800s although the rate of extraction has increased substantially in the last two decades. Well pads, roads, and infrastructure built to support resource development alter native vegetation configuration; however, the rate and effect of land cover change resulting from oil and gas extraction has not been quantified across the region. We used a Geographic Information System (GIS) to model development through time and assess change to native vegetation at two spatial extents (field and subbasin) within the Wyoming portion of the Wyoming Basins Ecoregional Assessment (WBEA) area. Since 1900, a minimum of 1,703 km2 of native vegetation in the WBEA area has been replaced by well pads or roads. Shrublands were, and continue to be, the dominant land cover class and the cover type most affected by oil and gas extraction. Average shrubland patch size has decreased by approximately 10% at the subbasin extent in the WBEA. Core area (≥60 m from edge) size declined by 13% as road development fragmented formerly continuous patches. To date, the majority of land cover change has occurred in formally identified oil and gas fields, which cover about 1% of the WBEA in Wyoming. Approximately 7.5% of shrubland within oil and gas fields has been converted to well pad or a road supporting a well, and shrubland patch size has declined by 45%. Resource reserves, especially natural gas, have been identified outside traditional fields, and development will likely expand as resource development becomes more cost-effective. Revegetation guidelines are in place for development areas addressed by Environmental Impact Assessments although no quantitative data are available to assess how well restoration efforts are restoring landscapes and connecting fragments.