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Background  While several studies have assessed the associations between biological factors and tuberculosis (TB) transmission, our understanding of the associations between TB transmission and social and economic factors remains incomplete. We aimed to explore associations between community TB transmission and socio-economic factors within a high TB-HIV burdened setting.    Methods  We conducted a cross-sectional molecular epidemiology study among adult patients attending a routine TB clinic. Demographic and clinical data were extracted from TB registers and clinical folders; social and economic data were collected using interviewer-administered questionnaires;  Mycobacterium tuberculosis  isolates were genotyped and classified as clustered/non-clustered using  IS 6110-based Restriction Fragment Length Polymorphism. Composite “social” and “economic” scores were generated from social and economic data. Data were analyzed using StataCorp version 15.0 software. Stratified, bivariable analyses were performed using chi-squared. Wilcoxon signed rank tests; univariable and multivariable logistic regression models were developed to explore associations in the social, economic, traditional and composite TB risk factors with TB transmission.    Results  Of the 505 patient  Mtb   strains, 348(69%) cases were classified as clustered and 157(31%) were non-clustered. Clustered cases were more likely to have lived longer in the study community, (odds ratio [OR] = 1.05, 95% Confidence interval [C.I]:1.02–1.09,  p  = 0.006); in the same house (OR = 1.04, C.I: 0.99–1.08,  p  = 0.06); and had increased household crowding conditions (i.e fewer rooms used for sleeping, OR = 0.45, C.I:0.21–0.95,  p  = 0.04). Although a higher proportion of clustered cases had a low economic score, no statistically significant association was found between clustering and either the economic score ( p  = 0.13) or social score ( p  = 0.26).    Conclusions  We report a novel association between  Mtb  transmission and prolonged stay within a high burdened community. Transmission was also associated with fewer rooms for sleeping in a household. Increased social interaction and prolonged residence in a high burdened community are important factors linked to  Mtb  transmission, possibly due to increased probability of higher effective contact rates. The possible importance of degrees of poverty within low socio-economic setting warrants further study.

TB transmission is associated with prolonged stay in a low socio-economic, high burdened TB and HIV community in Cape Town, South Africa