Addressing equity in healthcare is fundamental for delivering safe care to vulnerable patients, especially during COVID-19. This paper aims to identify barriers and enabling factors for general practitioners (GPs) in delivering safe and equitable care during the COVID-19 pandemic. Semi-structured interviews took place during May–July 2020 among 18 Flemish and 16 Dutch GPs. Thematic analysis of the interviews demonstrated that while GPs acknowledged a smooth information flow by governments and professional organizations on care guidelines, the fast-changing information challenged them to stay up to date. Media communication facilitated information dissemination but also fueled misinformation and miscommunication, creating unrealistic patient expectations. Certain guidelines and patient reluctance delayed necessary care. A shortage of personal protective equipment made GPs concerned about patient safety during face-to-face contacts. Teleconsultations became a popular alternative, but posed increased patient safety risks. GPs struggled to identify and reach vulnerable patients. Equitable care was hindered by time constraints; thus, having the appropriate materials facilitated such care. An interprofessional collaboration involving paramedical, social, and city services benefited patient safety and equity in healthcare. However, limitations in this collaboration pressured GPs. The unprecedented and resource-constrained environment challenged GPs’ capacity to provide the healthcare quality they aspired to deliver. A well-structured collaborative network involving all stakeholders could benefit safe and equitable care in future pandemics.