We have evaluated the spread of SARS-CoV-2 through Latin America and the Caribbean (LAC) region by means of a correlation between climate and air pollution indicators, namely, average temperature, minimum temperature, maximum temperature, rainfall, average relative humidity, wind speed, and air pollution indicators PM10, PM2.5, and NO2 with the COVID-19 daily new cases and deaths. The study focuses in the following LAC cities: Mexico City (Mexico), Santo Domingo (Dominican Republic), San Juan (Puerto Rico), Bogotá (Colombia), Guayaquil (Ecuador), Manaus (Brazil), Lima (Perú), Santiago (Chile), São Paulo (Brazil) and Buenos Aires (Argentina). The results show that average temperature, minimum temperature, and air quality were significantly associated with the spread of COVID-19 in LAC. Additionally, humidity, wind speed and rainfall showed a significant relationship with daily cases, total cases and mortality for various cities. Income inequality and poverty levels were also considered as a variable for qualitative analysis. Our findings suggest that and income inequality and poverty levels in the cities analyzed were related to the spread of COVID-19 positive and negative, respectively. These results might help decision-makers to design future strategies to tackle the spread of COVID-19 in LAC and around the world.