Ecosystem carbon (C) uptake is determined largely by C residence times and increases in net primary production (NPP). Therefore, evaluation of C uptake at a regional scale requires knowledge on spatial patterns of both residence times and NPP increases. In this study, we first applied an inverse modeling method to estimate spatial patterns of C residence times in the conterminous United States. Then we combined the spatial patterns of estimated residence times with a NPP change trend to assess the spatial patterns of regional C uptake in the United States. The inverse analysis was done by using the genetic algorithm and was based on 12 observed data sets of C pools and fluxes. Residence times were estimated by minimizing the total deviation between modeled and observed values. Our results showed that the estimated C residence times were highly heterogeneous over the conterminous United States, with most of the regions having values between 15 and 65 years; and the averaged C residence time was 46 years. The estimated C uptake for the whole conterminous United States was 0.15 P g C a−1. Large portions of the taken C were stored in soil for grassland and cropland (47–70%) but in plant pools for forests and woodlands (73–82%). The proportion of C uptake in soil was found to be determined primarily by C residence times and be independent of the magnitude of NPP increase. Therefore, accurate estimation of spatial patterns of C residence times is crucial for the evaluation of terrestrial ecosystem C uptake.