Skin infections caused by Streptococcus pyogenes are a significant health concern in the tropics and among Indigenous populations of developed countries. To study the immunobiology of skin infections and to develop preventative and therapeutic measures to target these infections, an in vivo model is vital. We developed a mouse model to investigate immunity to skin infections and for testing the efficacy of several vaccine candidates. This article describes the method of induction of superficial skin infections, their progression and regression, and processing of samples to obtain critical readouts and analyses. This model could be valuable to inform clinical studies.