Semiarid forests are very sensitive to climatic change and among the most difficult ecosystems to accurately model. We tested the performance of the Biome-BGC model against eddy flux data taken from young (years 2004–2008), mature (years 2002–2008), and old-growth (year 2000) ponderosa pine stands at Metolius, Oregon, and subsequently examined several potential causes for model-data mismatch. We used the Generalized Likelihood Uncertainty Estimation methodology, which involved 500,000 model runs for each stand (1,500,000 total). Each simulation was run with randomly generated parameter values from a uniform distribution based on published parameter ranges, resulting in modeled estimates of net ecosystem CO2 exchange (NEE) that were compared to measured eddy flux data. Simulations for the young stand exhibited the highest level of performance, though they overestimated ecosystem C accumulation (−NEE) 99% of the time. Among the simulations for the mature and old-growth stands, 100% and 99% of the simulations underestimated ecosystem C accumulation. One obvious area of model-data mismatch is soil moisture, which was overestimated by the model in the young and old-growth stands yet underestimated in the mature stand. However, modeled estimates of soil water content and associated water deficits did not appear to be the primary cause of model-data mismatch; our analysis indicated that gross primary production can be accurately modeled even if soil moisture content is not. Instead, difficulties in adequately modeling ecosystem respiration, mainly autotrophic respiration, appeared to be the fundamental cause of model-data mismatch.