Spontaneous pneumothorax and pneumomediastinum (SP–SPM) are relatively rare medical conditions that can occur with or independently of COVID-19. We conducted a retrospective analysis of SP–SPM cases presented to the emergency departments (EDs) of two University-affiliated tertiary hospitals from 1 March 2020 to 31 October 2022. A total of 190 patients were identified: 52 were COVID-19 cases, and 138 were non-COVID-19 cases. The primary outcome we were looking for was in-hospital mortality. The secondary outcomes concerned the disease severity assessed by (a) days of hospitalization; (b) required mechanical ventilation (MV); and (c) required intensive care (IC). All were investigated in the context of the five pandemic waves and the patients’ age and comorbidities. The pandemic waves had no significant effect on the outcomes of these patients. Logistic regression found age (OR = 1.043; 95%CI 1.002–1.085), COVID-19 (OR = 6.032; 95%CI 1.757–20.712), number of comorbidities (OR = 1.772; 95%CI 1.046–3.001), and ground-glass opacities over 50% (OR = 5.694; 95%CI 1.169–27.746) as significant risk predictors of in-hospital death while controlling for gender, smoking, the pandemic wave, and the extension of SP–SPM. The model proved good prediction performance (Nagelkerke R-square = 0.524) and would hold the same significant predictors for MV and IC.