Abstract Background Patterns of protective health behaviors, such as handwashing and sanitizing during the COVID-19 pandemic, may be predicted by macro-level variables, such as regulations specified by public health policies. Health behavior patterns may also be predicted by micro-level variables, such as self-regulatory cognitions specified by health behavior models, including the Health Action Process Approach (HAPA). Purpose This study explored whether strictness of containment and health policies was related to handwashing adherence and whether such associations were mediated by HAPA-specified self-regulatory cognitions. Methods The study (NCT04367337) was conducted among 1,256 adults from Australia, Canada, China, France, Gambia, Germany, Israel, Italy, Malaysia, Poland, Portugal, Romania, Singapore, and Switzerland. Self-report data on cross-situational handwashing adherence were collected using an online survey at two time points, 4 weeks apart. Values of the index of strictness of containment and health policies, obtained from the Oxford COVID-19 Government Response Tracker database, were retrieved twice for each country (1 week prior to individual data collection). Results Across countries and time, levels of handwashing adherence and strictness of policies were high. Path analysis indicated that stricter containment and health policies were indirectly related to lower handwashing adherence via lower self-efficacy and self-monitoring. Less strict policies were indirectly related to higher handwashing adherence via higher self-efficacy and self-monitoring. Conclusions When policies are less strict, exposure to the SARS-CoV-2 virus might be higher, triggering more self-regulation and, consequently, more handwashing adherence. Very strict policies may need to be accompanied by enhanced information dissemination or psychosocial interventions to ensure appropriate levels of self-regulation.