Assessing geographic patterns of species richness is essential to develop biological conservation as well as to understand the processes that shape these patterns. We aim to improve geographic prediction of tree species richness (TSR) across eastern USA by using: 1) gridded point-sample data rather than spatially generalized range maps for the TSR outcome variable, 2) new predictor variables (forest area FA; mean frost day frequency MFDF) and 3) regression models that account for spatial autocorrelation. TSR was estimated in 50 km by 50 km grids using Forest Inventory and Analysis (FIA) point-sample data. Eighteen environmental predictor variables were employed, with the most effective set selected by a LASSO that reduced multicollinearity. Those predictors were then employed in Generalized linear models (GLMs), and in Eigenvector spatial filtering (ESF) models that accounted for spatial autocorrelation. Models were evaluated by model fit statistics, spatial patterns of TSR predictions, and spatial autocorrelation. Our results showed gridded TSR was best-predicted by the ESF model that used, in descending order of influence: precipitation seasonality, mean precipitation in the driest quarter, FA, and MFDF. ESF models, by accounting for spatial autocorrelation, outperformed GLMs regardless of the predictors employed, as indicated by percent deviance explained and spatial autocorrelation of residuals. Small regions with low TSR, such as the Midwest prairie peninsula, were successfully predicted by ESF models, but not by GLMs or other studies. Gridded TSR in Florida was only correctly predicted by the ESF model with FA and MFDF, and was over-predicted by all other models.