Anthropogenic activities, by far the largest source of NOx into the atmosphere, induce a weekly cycle of NO2 abundances in cities. Comprehensive analysis of the 2005–2017 OMI NO2 dataset reveals significant weekly cycles in 115 of the 274 cities considered. These results are corroborated by a full year of high-resolution TROPOMI NO2 observations. The OMI dataset permits us to identify trends in the weekly cycle resulting from NOx emissions changes. The data show a clear weakening of the weekly cycle over European and U.S. cities, an evolution attributed to the decline in anthropogenic emissions and the resulting growing importance of background NO2, whereas NO2 lifetime changes also play a minor role. In particular, the Sunday NO2 columns averaged over all U.S. cities are found to increase, relative to the weekly average, from 0.72 during 2005–2007 to 0.88 in 2015–2017. The opposite tendency is recorded in regions undergoing rapid emission growth. Multiyear simulations over the U.S. and the Middle East using the chemistry-transport model MAGRITTEv1.1 succeed in capturing the observed weekly cycles over the largest cities, as well as the observed long-term trends in the weekly cycle.