Blinding trachoma is believed to be the end result of a long-term progressive scarring process that is initiated by recurrent infection by the bacterium Chlamydia trachomatis starting in childhood. Scar tissue predominantly develops on the inner surface of the upper eyelids (conjunctiva). However, the rates, drivers and pathophysiological determinants are poorly understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors in two cohorts of adults in Tanzania and Ethiopia. These groups of people already had a degree of scarring and were regularly followed-up with over a two-year period. We found scarring progressed in about a quarter of people over this time. The progression was closely associated with episodes of conjunctival inflammation but not to the detection of C. trachomatis infection. This raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates the likely need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level.