The cellular landscape of the human gastrointestinal tract is dynamic throughout life, changing in response to changing functional requirements and environmental exposures. While the human intestines has been explored in depth, we present a comprehensive single-cell analysis across gut regions, and throughout development, adulthood for the first time. Using single-cell RNAseq and VDJ analysis, we survey all cell lineages in the healthy developing, paediatric and adult human gut, including 347,980 cells from up to 10 distinct anatomical sites. We identify BEST4+ enterocytes throughout the gut and implicate Tuft cells in IgG sensing. We define novel cell populations in the developing enteric nervous system and show patterned expression of irritable bowel syndrome and Hirschsprung’s disease. In addition, we identify key cell players and communication networks initiating lymphoid structure formation in early human development. We show that lymphoid organogenesis programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation.