We demonstrate that a two-polariton blockade (2PB) can occur under resonant single-polariton driving in an atom-cavity system operating in the ultrastrong coupling (USC) regime-a phenomenon qualitatively distinct from, and unattainable in, both the strong and weak coupling regimes. In the USC regime, where the ratio of the atom-cavity coupling strength to the cavity resonance frequency exceeds 0.1, hybrid light-matter quasiparticles known as polaritons emerge. By employing modified second- and third-order correlation functions appropriate for the USC regime, we predict the emergence of 2PB, characterized by pronounced two-polariton bunching accompanied by suppressed three-polariton coincidences. This Letter introduces a novel route to achieving 2PB, with promising implications for the realization of multiparticle quantum light sources in the USC regime.