Interaction between parathyroid hormone/parathyroid hormone–related peptide receptor 1 (PTHR1) and low‐density lipoprotein receptor–related protein 6 (Lrp6) is important for parathyroid hormone (PTH) signaling and anabolic action. Because N‐cadherin has been shown to negatively regulate canonical Wnt/β‐catenin signaling, we asked whether N‐cadherin alters PTH signaling and stimulation of bone formation. Ablation of the N‐cadherin gene (Cdh2) in primary osteogenic lineage cells resulted in increased Lrp6/PTHR1 interaction in response to PTH_1‐34, associated with enhanced PTH‐induced PKA signaling and PKA‐dependent β‐catenin C‐terminus phosphorylation, which promotes β‐catenin transcriptional activity. β‐catenin C‐terminus phosphorylation was abolished by Lrp6 knockdown. Accordingly, PTH_1‐34 stimulation of Tcf/Lef target genes, Lef1 and Axin2, was also significantly enhanced in Cdh2‐deficient cells. This enhanced responsiveness to PTH extends to the osteo‐anabolic effect of PTH, as mice with a conditional Cdh2 deletion in Osx+ cells treated with intermittent doses of PTH_1‐34 exhibited significantly larger gains in trabecular bone mass relative to control mice, the result of accentuated osteoblast activity. Therefore, N‐cadherin modulates Lrp6/PTHR1 interaction, restraining the intensity of PTH‐induced β‐catenin signaling, and ultimately influencing bone formation in response to intermittent PTH administration. © 2014 American Society for Bone and Mineral Research.