COVID-19-related knowledge and behaviors remain essential for controlling the spread of disease, especially among vulnerable patients with advanced, chronic diseases. We prospectively assessed changes over 11 months in COVID-19-related testing, knowledge, and behaviors among patients with non-communicable diseases in rural Malawi using four rounds of telephone interviews between November 2020 to October 2021. The most commonly reported COVID-19-related risks among patients included visiting health facilities (35–49%), attending mass gatherings (33–36%), and travelling outside the district (14–19%). Patients reporting having experienced COVID-like symptoms increased from 30% in December 2020 to 41% in October 2021. However, only 13% of patients had ever received a COVID-19 test by the end of the study period. Respondents answered 67–70% of the COVID-19 knowledge questions correctly, with no significant changes over time. Hand washing, wearing face masks and maintaining a safe distance were the most frequently reported strategies to prevent the spreading of COVID-19. Wearing face masks significantly improved over time (p < 0.001). Although the majority reported accurate knowledge about COVID-19 and enhanced adherence to infection prevention measures over time, patients commonly visited locations where they could be exposed to COVID-19. Government and other stakeholders should increase COVID-19 testing accessibility to primary and secondary facilities.