The increased frequency of wildland fires (wildfires) poses a severe threat to the environment and human health, especially particulate matter (PM2.5) produced during wildfire events. Its effects and interactive effects with other factors on life expectancy are still poorly understood. The objective of this study is to examine the impact of wildfire smoke PM2.5, greenspace and terrain ruggedness as well as their interactive effects on the life expectancy at birth in the United States. The estimate of life expectancy in census tracts in the contiguous United States (US) during 2010 -2015 period was obtained from the US Centers for Disease Control and Prevention (CDC) using a small area estimation method. The number of smoke days, the concentration of smoke PM2.5, the percentage of forest and terrain ruggedness index were also obtained for each census tract during 2010-2011. The relationship between life expectancy and these environmental factors was examined with several models, including linear regression, multi-level regression, geographical weighted regression. The study found: (1) Life expectancy was significantly associated with the concentration of smoke PM2.5, the number of smoke days, and green space metrics. Specifically, our analysis revealed that for each 1 µg/m³ increase in smoke PM2.5 levels, life expectancy decreased by 1.2 years. Additionally, for every extra smoke day, life expectancy fell by 0.02 years. Conversely, a 1% increase in coverage of forest types—deciduous forest, mixed forest, or shrubland—resulted in an increase in life expectancy of 0.006, 0.009, 0.03, and 0.01 years, respectively. (2) The concentration of smoke PM2.5 has a consistent negative effect on life expectancy. (3) Greenspace measured by the percentage of forest might have a negative effect on life expectancy when it interacted with smoke PM2.5. (4) Terrain ruggedness has no significant effect on life expectancy. To sum up, our study suggests that smoke PM2.5 not only has a negative effect on life expectancy itself but also influences the beneficial impact of green space on life expectancy, may turning the interactive effects detrimental. The study provides new insights on the health effects of smoke PM2.5, which have implications in urban planning and public health policies.