Natural gas has become the largest fuel source for electricity generation in the United States and accounts for a third of energy production and consumption. However, the environmental and socioeconomic impacts across the supply chain and over the boom-and-bust cycle have not been comprehensively characterized. To provide insight for long-term decision making for energy transitions, we estimate the cumulative impacts of the shale gas boom in the Appalachian basin from 2004 to 2016 on air quality, climate change, and employment. We find that air quality impacts (1200 to 4600 deaths; $23B +99%/-164%) and employment impacts (469,000 job-years ±30%; $21B ±30%) follow the boom-and-bust cycle, while climate impacts ($12B to $94B) persist for generations well beyond the period of natural gas activity. Employment effects concentrate in rural areas where production occurs. However, almost half of cumulative premature mortality due to air pollution is downwind of these areas, occurring in urban regions of the Northeast. The cumulative temperature impacts of methane and carbon dioxide over a 30-year time horizon are nearly equivalent, but over the long term, the cumulative climate impact is largely due to carbon dioxide. We estimate that a tax on production of $2 per thousand cubic foot (+172%/-76%) would compensate for cumulative climate and air quality externalities across the supply chain.