Infection prevention and control (IPC) is an evidence-based approach used to reduce the risk of infection transmission within the healthcare environment. Effective IPC practices ensure safe and quality healthcare. The COVID-19 pandemic highlighted the need for enhanced IPC measures and the World Health Organization (WHO) emphasized the need for strict adherence to the basic principles of IPC. This paper aims to describe the IPC strategies implemented in general practice during the COVID-19 pandemic and to identify the factors that impact their adoption. Data were collected by means of an online self-reported questionnaire among general practices. Data from 4466 practices in 33 countries were included in the analysis. Our results showed a notable improvement in IPC during COVID-19 with more practices reporting that staff members never wore nail polish (increased from 34% to 46.2%); more practices reporting that staff never wear a ring/bracelet (increased from 16.1% to 32.3%); and more practices using a cleaning protocol (increased from 54.9% to 72.7%). Practice population size and the practice payment system were key factors related to adoption of a) range of IPC measures including patient flow arrangements and infrastructural elements. An understanding of the interplay between policy, culture, systemic supports, and behavior are necessary to obtain sustained improvement in IPC measures.