Fast-growing trees such as hybrid poplar (Populus spp.) are characterized by rapid growth and high biomass production. However, their tree productivity can vary depending on tree spacing, site conditions and genotype selection. In this study, we evaluated the impact of site × spacing × clone interaction on tree productivity. We selected plantations of four hybrid poplar clones (747215; Populus trichocarpa Torrey & A. Gray × P. balsamifera L., 915004, 915005; P. balsamifera × P. maximowiczii Henry and 915319; P. maximowiczii × P. balsamifera) established at three spacings (1 × 4 m, 2 × 4 m and 3 × 4 m) across three sites of contrasting productivity in northwestern Quebec, Canada. Increasing spacing from 1 × 4 m to 3 × 4 m led to larger stem and higher mean annual increment (MAI) and above-ground biomass on a per tree basis at the most productive site. In contrast, tree size remained smaller and unchanged across spacings at the least productive site, and for the least productive clone. The proportion of biomass allocated to the stem decreased when spacing increased from 1 × 4 m to 3 × 4 m to the benefit of branches. Hybrid poplar plantations’ productivity was promising, as MAI per hectare reached 20.10 m3 ha−1 year−1 at narrower spacing (1 × 4 m) at the most productive site for the most productive clone (915319). These findings highlight that site conditions modulate spacing effects and that high-yielding clones with optimal densities can maximize hybrid poplar productivity.