Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profiled 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE subjects, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unknown features of EoE. Active disease displayed enrichment of ALOX15+ macrophages, novel PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Receptor–ligand expression uncovered eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+Il13+ TH2 and endothelial cells as potential interactors of mast cells, which are likely play important roles in EoE pathogenesis. Resolution of inflammation-associated signatures included mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.