Nitrogen oxides (NOx = NO2 + NO) are a highly regulated species that play a major role in the formation of photochemical smog. While NOx emissions are generally decreasing over the U.S. as a result of more stringent environmental policies and improved emissions control technologies, the shale oil and natural gas industry is reversing this rate of changes in certain regions. We present here a quantitative analysis of NOx levels over the seven main U.S. shale plays (Bakken, Eagle Ford, Permian, Niobrara-Codell, Marcellus-Utica, Haynesville, and Barnett) between 2005 and 2015 using measurements of tropospheric NO2 from the Ozone Monitoring Instrument (OMI) aboard the NASA EOS-Aura aircraft. We develop and apply a methodology that seeks to maximise pollutant signals from oil and gas activities. For reference, we also examine the national trend averaged over the lower 48 states. Consistent with previous studies, we find NOx across the U.S. is generally declining. During the low-production phase of oil and natural gas production (2005–2009), we find declining trends in tropospheric NOx that are similar to the national trend (–4.6% yr–1) in 6 of the 7 study regions (–8 to –2% yr–1). In the high-production phase (2010–15), we find an increasing NOx trend in 5 of the 7 study basins (0.4 to 4.5% yr–1) while the national trend continued to decline (–0.3% yr–1). Over the most intensive oil-producing shale plays (Bakken, Eagle Ford, Permian and Niobrara-Codell), we observe a rapid growth (1–4.5% yr–1), which correlates well (r2 = 0.6–0.9) with their annual oil production rates and/or drilling rigs. In contrast, trends across the mainly gas-producing regions (Haynesville, Barnett, and Marcellus-Utica) show decreases (–0.4 to –1.7% yr–1) similar to the national trend, with the exception of the Marcellus-Utica where a slight increase (0.4 ± 0.2% yr–1) may be an indication of a small regional increase. Our study shows the important decadal effect that shale oil and natural gas operations has had on the tropospheric NO2 levels, and the potential consequences for regional air quality.