Several studies have examined the transmission dynamics of the novel COVID-19 disease in different parts of the world. Some have reported relationships with several environmental variables, suggesting that spread of the disease is enhanced in colder and drier climates. However, evidence is still scarce and mostly limited to a few countries, particularly from Asia. We examined the potential role of multiple environmental variables in COVID-19 transmission rates and patterns from February 23 to April 16 across 121 cities of Chile; this country covers a large climatic gradient (≈ 40º of latitude, ≈ 4,000 m of altitude and 5 climatic regions, from desert to tundra), but all cities share their social behaviour patterns and regulations. Our results indicated that COVID-19 transmission in Chile was mostly related to 3 main climatic factors (mean temperature, relative humidity and wind speed) and population size. Transmission was greater in colder and drier cities (although wind modulated the effect of temperature) and when wind speed was higher; finally, transmission increased with population size. The results of this study support some previous findings about the main environmental and demographic determinants of COVID-19 transmission, which may be useful for decision-making and management of the disease.