Global trends in tropospheric nitrogen dioxide (NO2) have changed dramatically in the past decade. Here, we investigate tropospheric NO2 variabilities over United States, Europe, and E. China in 2005–2018 to explore the mechanisms governing the variation of this critical pollutant. We found large uncertainties in the trends of anthropogenic nitrogen oxides (NOx) emissions, for example, the reductions of NOx emissions, derived with different approaches and data sets, are in the range of 35%–50% over the United States and 15%–45% over Europe in 2005–2018. By contrast, the analysis in this work indicates declines of anthropogenic NOx emissions by about 40% and 25% over the United States and Europe, respectively, in 2005–2018, and about 20% over E. China in 2012–2018. However, the shift of major NOx sources from power generation to industrial and transportation sectors has led to noticeable diminishing effects in emission controls. Furthermore, satellite measurements exhibit the influence of NO2 background levels over the United States and Europe, which offset the impacts of anthropogenic emission declines, resulting in flatter trends of tropospheric NO2 over the United States and Europe. Our analysis further reveals underestimation of background NO2 by chemical transport models, which can lead to inaccurate interpretations of satellite measurements. We use surface in-situ NO2 observations to diagnose the satellite-observed NO2 trends and find top-down NOx emissions over urban grids represent the changes in anthropogenic NOx emissions better. This work highlights the importance of comprehensive applications of different analysis approaches to better characterizing atmospheric composition evolution.