The rarity of rapid campaigns to characterize soils across scales limits opportunities to investigate variation in soil carbon stocks (SOC) storage simultaneously at large and small scales, with and without site-level replication. We used data from two complementary campaigns at 40 sites in the United States across the National Ecological Observatory Network (NEON), in which one campaign sampled profiles from closely co-located intensive plots and physically composited similar horizons, and the other sampled dozens of pedons across the landscape at each site. We demonstrate some consistencies between these distinct designs, while also revealing that within-site replication reveals patterns and predictors of SOC stocks not detectable with non-replicated designs. Both designs demonstrate that SOC stocks of whole soil profiles vary across continental-scale climate gradients. However, broad climate patterns may mask the importance of localized variation in soil physicochemical properties, as captured by within-site sampling, especially for SOC stocks of discrete genetic horizons. Within-site replication also reveals examples in which expectations based on readily explained continental-scale patterns do not hold. For example, even wide-ranging drainage class sequences within landscapes do not duplicate the clear differences in profile SOC stocks across drainage classes at the continental scale, and physicochemical factors associated with increasing B horizon SOC stocks at continental scales frequently do not follow the same patterns within landscapes. Because inferences from SOC studies are a product of their context (where, when, how), this study provides context—in terms of SOC stocks and the factors that influence them—for others assessing soils and the C cycle at NEON sites.