The coronavirus pandemic has infected more than 100 million people worldwide with COVID-19, with millions of deaths across the globe. In this research, we explored the effects of environmental and weather variables with daily COVID-19 cases and COVID-19 fatalities in Istanbul, Turkey. Turkey has the 8th highest number of COVID-19 cases globally, with the highest infections and deaths in Istanbul. This may be the first study to conduct a comprehensive investigation for environmental quality (air quality pollutants, e.g., PM2.5 and PM10, ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, etc.), weather parameters (temperature, humidity) and COVID-19 in Turkey. The authors collected meteorological data from 11 March 2020 to 8 February 2021 and COVID-19 data from Istanbul and other regions. The results from empirical estimations, correlation analysis, and quantile on quantile techniques support that air quality and temperature significantly influence COVID-19 deaths in Istanbul. This research may help policymakers and health scientists to take specific measures to reduce the spread of coronavirus across different global cities. The effects of air quality on COVID-19 in Istanbul was investigated. The study applied correlation and quantile on quantile techniques over daily data. Temperature significantly induces the spread of COVID-19 in Istanbul at all quantiles. Air quality and Nitrogen are positively linked with COVID-19 new cases.