The use of autograft skin is essential in the treatment of full thickness burns and large cutaneous defects. Both autograft thickness and condition of the wound bed modulate aesthetic and functional outcomes. Thicker autografts contract less and maintain greater functionality as the scar matures. The presence of hypodermis can also positively affect the eventual appearance and functionality of the wound site by modulating contraction and alleviating inflammation and cellular stress responses. In this study, we characterize wound-site physical and cellular characteristics following split-thickness skin grafting onto hypodermis vs. onto fascia. Compared to autografts grafted onto fascia, identical thickness autografts grafted onto fat demonstrated reduced contraction, enhanced mobility and vascularity, and reduced topographical variability. Grafts onto fat also showed reduced levels of myofibroblasts and leukocytic infiltration. The status of the wound bed prior to engraftment is an important contributor of skin quality outcome. The presence of hypodermis is associated with improved functional and aesthetic qualities of split thickness skin grafts, which are correlated with reduced presence of myofibroblasts and leukocytic infiltration.