We analyzed 13 years (1992−2004) of CO2 flux data, biometry, and meteorology from a mixed deciduous forest in central Massachusetts. Annual net uptake of CO2 ranged from 1.0 to 4.7 Mg-C ha−1yr−1, with an average of 2.5 Mg-C ha−1yr−1. Uptake rates increased systematically, nearly doubling over the period despite forest age of 75–110 years; there were parallel increases in midsummer photosynthetic capacity at high light level (21.5−31.5 μmole m−2s−1), woody biomass (101−115 Mg-C ha−1 from 1993−2005, mostly due to growth of one species, red oak), and peak leaf area index (4.5−5.5 from 1998–2005). The long-term trends were interrupted in 1998 by sharp declines in photosynthetic capacity, net ecosystem exchange (NEE) of CO2, and other parameters, with recovery over the next 3 years. The observations were compared to empirical functions giving the mean responses to temperature and light, and to a terrestrial ecosystem model (IBIS2). Variations in gross ecosystem exchange of CO2 (GEE) and NEE on hourly to monthly timescales were represented well as prompt responses to the environment, but interannual variations and long-term trends were not. IBIS2 simulated mean annual NEE, but greatly overpredicted the amplitude of the seasonal cycle and did not predict the decadal trend. The drivers of interannual and decadal changes in NEE are long-term increases in tree biomass, successional change in forest composition, and disturbance events, processes not well represented in current models.