Trends and transitions in the growing season MODerate resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) time series at 250-m resolution were analyzed for the period from 2000 to 2018 to understand recent patterns of vegetation change in ecosystems of the Yukon River basin in interior Alaska. Statistical analysis of changes in the NDVI time series was conducted using the “Breaks for Additive Seasonal and Trend” method (BFAST). This structural change analysis indicated that NDVI breakpoints and negative 18-yr trends in vegetation greenness over the years since 2000 could be explained in large part by the impacts of severe wildfires, commonly affecting shrubland and forested ecosystems at relatively low elevations (< 300 m). At least one NDVI breakpoint was detected at 29% of the MODIS pixels within the Yukon River basin study area. The warmest and wettest years in the study time period were found to be associated with a sizeable fraction (30%) of NDVI breakpoints. Among pixels with no NDVI breakpoints detected, both forest and shrubland trends were strongly skewed toward positive trend values. Results from gradual NDVI trend analysis supported the hypothesis that air temperature warming has enhanced the rates of (unburned) vegetation growth in shrubland and woodlands across interior Alaska over the past two decades.