The net primary productivity (NPP) of vegetation is an important indicator reflecting the vegetation dynamics and carbon sequestration capacity in a region. In recent years, China has implemented policies to carry out ecological protection. To understand the changes in the distribution of vegetation NPP in China and the influence of climate factors, the Carnegie–Ames–Stanford approach (CASA) model was used to estimate the NPP from 2001 to 2020. In this paper, several sets of measurement datasets and products were collected to evaluate the effectiveness of the model and suggestions were provided for the modification of the CASA model based on the evaluation results. In addition to the correlation analysis, this paper presents a statistical method for analyzing the quantitative effects in individual climatic factors on NPP changes in large regions. The comparison found that the model has a better estimation effect on grassland and needleleaf forest. The estimation error for the evergreen needleleaf forest (ENF) and deciduous broadleaf forest (DBF) decreases with the warming of the climatic zone, while the evergreen broadleaf forest (EBF) and deciduous needleleaf forest (DNF) do the opposite. The changes in total CASA NPP were consistent with the trends of other products, showing a dynamic increasing trend. In terms of the degree of correlation between the NPP changes and climatic factors, the NPP changes were significantly correlated with temperature in about 10.39% of the vegetation cover area and with precipitation in about 26.92% of the vegetation cover area. It was found that the NPP variation had a negative response to the temperature variation in Inner Mongolia grasslands, while it had a positive but small effect (±10 g C) in the Qinghai–Tibet Plateau grasslands. Precipitation had a facilitative effect on the grassland NPP variation, while an increase in the annual precipitation of more than 200 mm had an inhibitory effect in arid and semi-arid regions. This study can provide data and methodological reference for the ecological assessment of large-scale regional and climate anomalous environments.