Specific gravity is an important consideration for traditional uses of hybrid poplars for pulp and solid wood products, as well as for biofuels and bioenergy production. While specific gravity has been shown to be under strong genetic control and subject to within-tree variability, the role of genotype × environment interactions is poorly understood. Most specific gravity reports are for a limited number of locations, resulting in a lack of information about the interactions between clones and sites over a wide range of climate and soil conditions. The objective of the current study was to characterize the effects of bole position, site, clone, and site × clone interactions for twelve hybrid poplar genotypes grown in Iowa, Minnesota, Wisconsin, and Michigan, USA. Observed specific gravities ranged from 0.267 to 0.495 (mean = 0.352 ± 0.001 for 612 samples taken from 204 trees), with bole position and site × clone interactions having significant effects on specific gravity. Further investigation of the site × clone interactions indicated that environmental conditions related to water stress were key predictors of specific gravity. These data are important for informing genotypic selection and silvicultural management decisions associated with growing hybrid poplars.