Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 470 million people and resulted in more than 6 million deaths, and despite the availability of multiple vaccines, the world still faces many challenges with their rollout and waning efficacy in the face of emerging viral variants. Here, we use the high-density microarray patch (HD-MAP), developed by Vaxxas Pty Ltd, to deliver a SARS-CoV-2 spike subunit vaccine directly to the skin. We show that the vaccine is thermostable on the patches, with patch delivery enhancing both cellular and antibody immune responses. Elicited antibodies potently neutralize clinically relevant isolates including the Alpha, Beta, Delta, Gamma, Kappa, Lambda and Omicron variants. Last, a single dose of HD-MAP–delivered spike provided complete protection from a lethal virus challenge in an ACE2-transgenic mouse model. Collectively, these data show that HD-MAP delivery of a SARS-CoV-2 vaccine was superior to traditional needle-and-syringe vaccination and may be a significant addition to the ongoing COVID-19 (coronavirus disease 2019) pandemic.