Existing research recognizes the COVID-19 impact on waste generation. However, the preliminary studies were made at an early pandemic stage, focused on the household waste fraction, and employed descriptive statistics that lacked statistical support. This study tries to fill this gap by providing a reliable statistical analysis setting inferential confidence in the waste generation differences found in Castellón. Repeated measures ANOVA were carried out for all the waste fractions collected and recorded in the city landfill database from 2017 to 2020. Additionally, Bonferroni’s multiple comparison test (p < 0.05) was used to assure confidence level correction and identify which pairs of years’ differences appeared. The longitudinal study identified trends for each waste fraction before the pandemic and showed how they changed with the advent of the crisis. Compared to 2019, waste collection in 2020 significantly grew for glass and packaging; remained unchanged for beaches, paper and cardboard, and dropped substantially for households, streets, markets, bulky waste, hospitals, and recycling centres. Total waste showed no differences between 2017 and 2019 but dropped significantly in 2020. These findings may help us better understand the long-term implications of COVID-19 and improve municipal solid waste management in a similar crisis.