Soil organic matter (SOM) is the largest terrestrial pool of organic carbon (C), and potential carbon-climate feedbacks involving SOM decomposition could exacerbate anthropogenic climate change. Despite the importance of SOM in the global C cycle, our understanding of the controls on SOM stabilization and decomposition is still developing, and as such, SOM dynamics are a source of major uncertainty in current Earth system models (ESMs), which reduces the effectiveness of these models in predicting the efficacy of climate change mitigation strategies. To improve our understanding of controls on SOM decomposition at scales relevant to such modeling efforts, A and upper B horizon soil samples from 22 National Ecological Observatory Network (NEON) sites spanning the conterminous U.S. were incubated for 52 weeks under conditions representing site-specific mean summer temperature and horizon-specific field capacity (-33 kPa) water potential. Cumulative CO2 respired was periodically measured and normalized by soil organic C content to obtain cumulative specific respiration (CSR). A two-pool decomposition model was fitted to the CSR data to calculate decomposition rates of fast- (kfast) and slow-cycling pools (kslow). Post-LASSO best subsets multiple linear regression was used to construct horizon-specific models of significant predictors for CSR, kfast, and kslow. Significant predictors for all three response variables consisted mostly of proximal factors related to clay-sized fraction mineralogy and SOM composition. Non-crystalline minerals and lower SOM lability negatively affected CSR for both A and B horizons. Significant predictors for decomposition rates varied by horizon and pool. B horizon decomposition rates were positively influenced by nitrogen (N) availability, while an index of pyrogenic C had a negative effect on kfast in both horizons. These results reinforce the recognized need to explicitly represent SOM stabilization via interactions with non-crystalline minerals in ESMs, and they also suggest that increased N inputs could enhance SOM decomposition in the subsoil, highlighting another mechanism beyond shifts in temperature and precipitation regimes that could alter SOM decomposition rates.