ObjectivesPrevious cohort studies have reported the significant association between tooth loss and functional disability in aging adults. This study aimed to examine whether eating and communication difficulties mediate this association. MethodsData from wave 7 (2014–2015) to wave 8 (2016–2017) of the English Longitudinal Study of Ageing (ELSA) were analyzed. Severe tooth loss was defined as “< 20 teeth remaining” at baseline. Eating and communication difficulties were assessed through a questionnaire. Onset of functional disability 2-year later was assessed by activities of daily living (ADL) scale and instrumental ADL (IADL) scale. Baron and Kenny’s causal steps and Karlson/Holm/Breen (KHB) method were used to examine the mediating effect. ResultsAt baseline, 7,830 participants had no ADL disability and 7,678 participants had no IADL disability. The 2-year cumulative incidence of ADL disability and IADL disability were 7.5 % and 9.0 %, respectively. Severe tooth loss was associated with both incidence of ADL disability (OR = 1.40; 95 % CI = 1.13–1.74) and incidence of IADL disability (OR = 1.24; 95 % CI = 1.01–1.52). The mediating effect of eating difficulty on the association between severe tooth loss and ADL disability was 1.04 (95 % CI: 1.01, 1.06). The mediating effect of communication difficulty on the association between severe tooth loss and IADL disability was 1.05 (95 % CI: 1.02, 1.07). ConclusionSevere tooth loss is associated with incidence of functional disability in middle-aged and older English adults. Eating and communication difficulties play the role as mediators in these associations. Clinical SignificanceThis prospective study contributes to elucidating parts of biological mechanism underlying tooth loss and functional disability in middle-aged and older adults. It suggests that oral health strategies aimed to protect teeth may be important in reducing the risk of functional disability.