The aim of this project is to explore perceptions towards and adherence to COVID-19 public health preventive measures in Indigenous communities within Northwest Territories, Canada. Utilizing a cross-sectional study design the project took place within ten Northwest Territories communities between 1st April and 30th November 2021. Convenience sampling methods were utilized and adhered to public health restrictions. Self-identifying Indigenous adults (≥ 18 years old) were invited to complete a semi-structured interviewer-administered questionnaire. Participants (n = 287; 33.1% men, 66.6% women) had a mean age of 41.6 years (SD ± 13.5). Preventive measures were practiced by 98.6% of participants. Most participants reported often or always practicing three measures: avoiding gatherings (67.2%), avoiding usual greetings (63.3%), and limiting contact with high-risk individuals (71.4%). Most participants reported rarely/never practicing self-isolation (67.5%) and self-quarantining (76.5%) measures. Significant associations existed between the August 2021 COVID-19 outbreak and self-quarantining (p = 0.0023), self-isolating (p = 0.0023), and going onto the land (p = 0.0001). Participants found masking and travel restrictions challenging. Sadness and loneliness resulted from limited access to Elders. Kinship and community safety were important to Indigenous community members and influenced COVID-19 preventive measure utilization. The findings can inform culturally specific COVID-19 public health policy development.