From 2008 to mid-2016, there was more than a 7-fold increase in oil production and nearly a tripling of natural gas production in the Colorado Denver–Julesburg Basin (DJB). This study utilized air samples collected at the Boulder Atmospheric Observatory (BAO) tower in southwestern Weld County in the DJB to investigate atmospheric mole fraction trends of methane and volatile organic compounds (VOCs). Elevated methane and propane mole fractions and low values (<1) in the ratio of i-pentane to n-pentane at BAO were found to be associated with flow patterns that transport air from the northeast (NE) to east (E) sector to the site, the direction where the primary locations of oil and natural gas (O&NG) extraction and processing activities are located. Median mole fractions of the O&NG tracer propane at BAO were 10 times higher than background values when winds came from the NE quadrant. This contrasts with lower mole fractions of O&NG-related constituents in air parcels arriving at BAO from the south, the direction of the major urban area of Denver. None of O&NG tracers, for example, methane and propane, show statistically significant trends in mole fraction (relative to the background) over the study period in air transported from the DJB. Also, longer term acetylene mole fraction changes were not seen in NE quadrant or south sector samples. A significant decline in the mole fraction ratio of i-pentane to n-pentane in the NE sector data provides evidence of an increasing influence of O&NG on the overall composition of VOCs measured at BAO, a change not seen in measurements from the south (urban) sector. These results suggest that O&NG emissions and resulting atmospheric mole fractions have remained relatively constant over 2008–2016. The behavior in the observations is in contrast to the most recent VOC emissions inventory. While the inventory projects O&NG total VOC emission reductions between 2011 and 2020, of –6.5% per year despite the large production increases, the best estimate of the propane emission rate of change for the DJB-filtered data during 2008–2016 is much smaller, that is, –1.5% per year.