Background/Objective: Stress may affect patients with atopic dermatitis (AD). The aim of this study was to examine the impact of the COVID-19 pandemic and the earthquake in Zagreb, Croatia (March 2020), on AD patients and their disease severity, symptoms/itch, and perceived stress. Methods: Our observational cross-sectional study included three groups of AD patients diagnosed by a physician: group 1 (n = 50), who experienced both the pandemic (quarantine) and the earthquake; group 2 (n = 50), who experienced only the pandemic; and group 3 (n = 50), the comparison group, who experienced neither disaster (patients examined 2018–2019). Groups 1 and 2 were examined May–June 2020, immediately after the national lockdown/quarantine. Disease severity (SCORAD), data from the Perceived Stress Scale (PSS), and information on patients’ confirmed allergies were recorded for all groups, while groups 1 and 2 additionally completed a questionnaire concerning their disease, hand hygiene, and experience during the pandemic and/or earthquake. Results: The patients exposed to both disasters reported more pronounced AD worsening (p < 0.001; r = 0.388) and more frequent itching (p < 0.001; r = 0.350) than those exposed to the pandemic only. Notably, we found certain differences by gender: during the pandemic, women significantly more frequently washed their hands (81% of women washed “very frequently,” while 52% of men washed “quite often”) and had significantly higher PSS levels than men (p < 0.05). Concerning allergies, present or absent, during the pandemic, there was no significant difference in SCORAD between groups 1 and 2, neither when analyzed separately for indoor nor for outdoor allergens. The most commonly reported psychological disturbances during the pandemic were concern (46%), anger (18%), anxiety (16%), depression (9%), and increased alcohol, cigarette, and opioid agent use (6%). Conclusion: The COVID-19 pandemic together with the earthquake significantly increased disease severity and influenced AD worsening, itching, and psychological disturbances. This indicates that stressful events meaningfully affect the course of AD.