Addressing the transmission enigma of the neglected disease Buruli ulcer (BU) is a World Health Organization priority. In Australia, we have observed an association between mosquitoes harboring the causative agent, Mycobacterium ulcerans, and BU. Here we tested a contaminated skin model of BU transmission by dipping the tails from healthy mice in cultures of the causative agent, Mycobacterium ulcerans. Tails were exposed to mosquito (Aedes notoscriptus and Aedes aegypti) blood feeding or punctured with sterile needles. Two of 11 of mice with M. ulcerans contaminated tails exposed to feeding A. notoscriptus mosquitoes developed BU. Eighteen of 20 mice subjected to contaminated tail needle puncture developed BU. Mouse tails coated only in bacteria did not develop disease. We observed a low infectious dose-50 of four colony-forming units and a median incubation time of 12 weeks, consistent with data from human infections. We have uncovered a highly efficient and biologically plausible atypical transmission mode of BU via natural or anthropogenic skin punctures.