Diabetic foot ulcers (DFUs) are a growing burden on patients and health care systems that often require multiple treatments of both conventional and advanced modalities to achieve complete wound closure. A novel autologous homologous skin construct (AHSC) has been developed to treat cutaneous defects with a single topical application, by leveraging the endogenous repair capabilities of the patient's healthy skin. The AHSC's ability to close DFUs with a single treatment was evaluated in an open‐label, single‐arm feasibility study. Eleven patients with DFUs extending up to tendon, bone, or capsule received a single topical application of AHSC. Closure was documented weekly with high‐resolution digital photography and wound planimetry. All 11 DFUs demonstrated successful graft take. Ten DFUs closed within 8 weeks. The median time‐to‐complete closure was 25 days. The mean percent area reduction for all 11 wounds at 4 weeks was 83%. There were no adverse events related to the AHSC treatment site. This pilot study demonstrated AHSC may be a viable single application topical intervention for DFUs and warrants investigation in larger, controlled studies.