Global trends in the demand for forest products, decreasing total area of actively managed forests, and pressures to increase profit margins suggest that forest management intensity will continue to increase in the future. These trends have typically led to shorter rotation lengths and increased utilization of forest biomass to supply the bio-economy with feedstocks for energy, novel bio-chemicals, traditional pulp and paper, panels and solid forest products. The combined influence of increased utilization and shortened rotation lengths have raised concerns regarding potential soil nutrient depletion and corresponding reductions in site productivity. In response to these concerns, the Weymouth Point Study Area (WPSA) in north-central Maine was established in a spruce-fir forest in 1979 to quantify the effects of whole-tree harvesting (WTH) and stem-only harvesting (SOH) on nutrient cycling and site productivity in adjacent, paired watersheds with large fixed-area plots. From 1979 to 2016, 49 permanent sample plots were established across three soil drainage classes to evaluate tree- and stand-level growth and nutrition response to harvest residue management and silviculture practices. Harvest treatments were implemented in 1981 with SOH simulated by returning delimbing residues after WTH, including chipped tops, branches and foliage (CHP), and lopped-and-scattered residues (LOP). The harvested watershed was aerially treated with triclopyr herbicide in the fourth growing season following WTH to release naturally regenerated conifers from herbaceous and woody weed competition. Response to silviculture practices were evaluated following pre-commercial thinning (PCT) and the addition of ammonium-nitrate fertilizer (FERT) treatments initiated 10 and 12 years following WTH, respectively. Thirty-five years post-harvest, tree growth and nutrient uptake have not been significantly affected by WTH at this location. Mean tree size was positively influenced by PCT; however, FERT did not significantly affect mean tree size. There were also no significant effects of treatments on aboveground biomass production and net nutrient uptake in trees. These results suggest that WTH at final felling for bio-economy feedstock production in spruce-fir forests similar to those at the WPSA (Chesuncook catena soils) is sustainable. However, this hypothesis is based on mid-rotation assessment of tree growth as an indicator of sustainable forest management. Further research is required to confirm the absence of negative impacts on tree- and stand-level growth and nutrition through the end of the current rotation.