Gasdermin-D (GSDMD) is activated by caspase cleavage at (GSDMD 1–275) to form membrane pores, leading to unconventional secretion of proinflammatory cytokines. Viral proteases are essential intracellular enzymes that cleave viral polyproteins for replication. In addition, the SARS-CoV-2 3C-like protease (3CLpro or Mpro) cleaves a diverse array of intracellular host proteins for immune and antiviral defence evasion.As no viral proteases are reported to be extracellular, exploring extracellular substrates of viral proteases has been overlooked. We establish that 3CLpro and nucleocapsid protein are secreted from SARS-CoV-2 infected cells by unconventional protein secretion through GSDMD and GSDME pores formed by viral 3CLpro in concert with host caspase cleavages. 3CLpro cleaves gasdermin-D (GSDMD) at LH270↓271NF, generating a pore-forming N-terminal domain (GSDMD 1–270) and leading to 3CLpro release from cells. Non-cleavable mutant GSDMD established the relative contributions of caspase and 3CLpro cleavage events. Excessive GSDMD 1–270 pore formation increased lactate dehydrogenase release, indicative of pyroptotic cell death in concert with cell membrane lytic rupture. Glycine cytoprotection prevented lysis, resulting in increased GSDMD-mediated 3CLpro secretion. 3CLpro was abundant in conditioned media of SARS-CoV-2-infected cells and was detected in bronchoalveolar lavage fluid of wild-type SARS-CoV-2-infected mice and decreased in Gsdmd–/–Gsdme–/– mice. Extracellular 3CLpro retained proteolytic activity in serum, dampened platelet activation and aggregation, and inactivated interferon-l1 by two cleavages. Linking intracellular 3CLpro cleavage of GSDMD with 3CLpro secretion and extracellular activity reveals unexpected viral protease-driven immune evasion mechanisms. To the best of our knowledge, the secretion of a viral protease with potential pathologic consequences has not been reported previously, and so our work should stimulate similar studies in other viral infections and uncover unexplored mechanisms of viral pathogenesis and drug targeting modalities.