Accidental escapes of pathogens from laboratories continue to cause outbreaks in the community today, posing significant risks to the general public, animal communities and the environment. These incidents, as well as the uncertainties surrounding the origins of the COVID-19 pandemic, highlight the need to consider unnatural origins as part of emerging outbreak surveillance and detection. Identifying recurring patterns and distinctive factors of laboratory-associated disease outbreaks can aid in successfully preventing and mitigating these occurrences. Seventy incidents of laboratory-associated leaks that led to outbreaks in the wider public have been reported (Supplementary Appendix S1). Seven renowned cases that have been comprehensively studied were selected for review: (i) 1955 Polio vaccine incident in western USA, (ii) 1977 H1N1 influenza virus re-emergence in China and the Soviet Union, (iii) 1979 Anthrax release in Sverdlovsk, Soviet Union, (iv) 1995 Venezuelan equine encephalitis epidemics in Venezuela and Colombia, (v) 2003–4 SARS-CoV-1 escapes from Singapore, Taiwan and China, (vi) 2007 Foot-and-Mouth disease virus outbreak in Pirbright, England and (vii) 2019 Brucella leak in Lanzhou, China. These outbreaks were selected because data on their geographical spread, genetics, phylogeny, epidemiological factors (including attack rates, infectious dose, time, location and season of spread) and governmental and institutional responses to the incidents had been previously analysed and published. Thematic analysis of these lines of evidence revealed seven recurring insights described in historically confirmed laboratory-associated outbreaks: unusual strain characteristics, peculiar clinical manifestations or affected demographics, unusual geographical features, atypical epidemiological patterns, delayed government action and communication to the public, misinformation and disinformation spread to the public and biosafety concerns/incidents predating the event. The outbreaks exhibited between 13 and 19 retrospectively identified indicators. These indicators were used to develop preliminary risk criteria intended to support structured, hypothesis-generating assessment of outbreaks, rather than to establish origin.