Poplars (Populus spp.) are among the most productive tree species in the northern hemisphere, displaying fast-growth across a wide geoclimatic range. Climate change and alterations in precipitation regimes can affect the distribution of forest trees and poplars are one of the most sensitive woody plants to water stress due to their naturally high transpiration rates; thus, drought can significantly limit the productivity of poplar trees. Cuticular wax is critical in preventing non-stomatal water loss, and its composition varies depending on tissue type, age, and species, as well as in response to diverse biotic and abiotic stresses. Genome-wide association studies can reveal a genomic response to phenotypic selection by analyzing the genetic variation occurring in the genomes of several individuals. In this study, the wax profiles of P. trichocarpa leaves were analyzed to determine the phenotypic variations between common clones grown under drought vs. non-drought conditions to examine the natural variation in wax composition. In addition, poplar clones grown in different common gardens were compared to determine whether there are inherent differences in the wax composition. Specifically, leaf wax was analyzed by GC-FID to determine the variation in the cuticular wax composition among clones and a GWAS was completed on wax traits/phenotypes. Although the total amount of wax did not change in response to drought stress, wax components such as alkenes, alcohols, and esters changed. The common garden influence, on the other hand, was found to produce considerable variations in both total wax load and wax components. Following drought treatment, GWAS revealed that two genes connected to alkanes, Potri.014G152600 (CER1) and Potri.018G072700 (FATB) which are known to play a role in wax biosynthesis. This information could be employed to select for drought-tolerant poplar genotypes in breeding programs.