Plant UDP-glycosyltransferases (UGT) transfer sugars to small acceptor molecules and thereby play key roles in the biosynthesis of secondary metabolites, including phenylpropanoids. Some of those metabolites are involved in the xylem lignification of a broad range of terrestrial plants, particularly trees. Here, we focused on poplar UGT72B37, coding for an enzyme glycosylating monolignols by investigating CRISPR/Cas9 mutant lines. The cell wall characterization revealed a 10% lignin content increase in the xylem of three-month-old mutant lines compared to the wild type. No ectopic lignification was evidenced in the pith of the stems of the mutants, suggesting that the increased lignin deposition is restricted to lignified cell walls. The analysis of the expression level of lignin biosynthesis and polymerization genes did not show significant changes between the WT and the ugt72b37 mutants, except for CINNAMOYL-COA REDUCTASE 2 which was significantly upregulated by 1.2–1.5-fold. Noticeably, UGT72B38, the closest related gene to UGT72B37, is upregulated in mutant lines, suggesting a functional compensation between UGT72B37 and UGT72B38 possibly linked with lignin biosynthesis and accumulation in poplar. Overall, these results reinforce a plausible role of monolignol glycosylation in the cell wall lignification process.