Introduction: The increasing number of pedestrian fatalities has emerged as a significant public health concern, a situation that has been exacerbated by the disruptions resulting from the COVID-19 pandemic. While existing literature provides insights into general trends and factors affecting pedestrian safety, a gap remains in understanding how these dynamics shifted during the pandemic and late-pandemic periods. This study aims to conduct a comprehensive assessment of the factors that have differential impacts on pedestrian fatalities across three periods: pre-pandemic (2018–2019), pandemic (2020–2021), and late-pandemic (2022) in comparison to the baseline period (2016–2017). Method: The data were obtained from various sources, including the Fatality Analysis and Reporting System, Centers for Disease Control and Prevention, Smart Location Database, and Disadvantaged Community Database. This study utilized a twofold approach: first, analyses were conducted at the pedestrian fatality level using a mixed effects multinomial logit model that compared the likelihood of a pedestrian fatality occurring in each study period; second, analyses were conducted at the census tract level using mixed effects negative binomial models that compared the frequency of pedestrian fatality across the study period. Results: The results showed pedestrian and driver age, impairment, jaywalking, weekend evenings/nights, and population density exhibited a temporal shift across the study periods and were associated with a higher likelihood of pedestrian fatalities. Furthermore, urban areas, lower-income neighborhoods, transit stop density, auto-oriented road network density, and percent population with poor mental health, were associated with an incremental increase in pedestrian fatalities across the study periods. Conclusions: This study highlights significant shifts in factors affecting pedestrian fatalities during and in the late-pandemic periods, underscoring the need for targeted safety interventions and infrastructure improvements. Practical applications: The findings suggest targeted pedestrian safety campaigns, improved traffic control, promoting safe behaviors, and infrastructure enhancements in low-income areas could mitigate pedestrian fatalities.