This work studied the spread of COVID-19, the meteorological conditions and the air quality in a megacity from two viewpoints: (1) the correlation between meteorological and air quality (PM10 and NO2) variables with infections and deaths due COVID-19, and (2) the improvement in air quality. Both analyses were performed for the pandemic lockdown due to COVID-19 in the City of Buenos Aires (CABA), the capital and the largest city in Argentina. Daily data from temperature, rainfall, average relative humidity, wind speed, PM10, NO2, new cases and deaths due COVID-19 were analyzed. Our findings showed a significant correlation of meteorological and air quality variables with COVID-19 cases. The highest temperature correlation occurred before the confirmation day of new cases. PM10 presented the highest correlation within 13 to 15 days lag, while NO2 within 3 to 6 days lag. Also, reductions in PM10 and NO2 were observed. This study shows that exposure to air pollution was significantly correlated with an increased risk of becoming infected and dying due to COVID-19. Thus, these results show that the NO2 and PM10 levels in CABA can serve as one of the indicators to assess vulnerability to COVID-19. In addition, decision-makers can use this information to adopt strategies to restrict human mobility during the COVID-19 pandemic and future outbreaks of similar diseases in CABA.