Elevated expression and activity of the non-receptor tyrosine kinase c-Src are associated with poor prognosis in breast cancer. However, while c-Src is considered a potential therapeutic target, the mechanisms by which it contributes to mammary tumourigenesis remain poorly characterized. The recent implication of c-Src in resistance to targeted therapies has emphasized the need to understand these mechanisms more completely. We have developed novel transgenic mouse models allowing conditional c-Src ablation specifically in the mammary epithelium with simultaneous expression of activated ErbB2 or polyomavirus middle-T antigen (PyV mT). In both models, mammary epithelial c-Src knockout significantly delays tumourigenesis and severely impairs tumour growth. Surprisingly, the requirement for c-Src in metastasis is context-dependent, since c-Src is completely dispensable for lung metastasis in ErbB2-driven tumours but its ablation severely impairs lung metastasis driven by PyV mT. Biochemical and gene expression analysis has emphasized the importance of metabolic regulation by c-Src in breast cancer cells, with c-Src-deficient tumours exhibiting significant impairments in mitochondrial structure and metabolism. Strikingly, we also find that c-Src ablation reduces the expression of components of Polycomb Repressor Complex 2 (PRC2), a key epigenetic regulator. Acquired resistance to Lapatinib in ErbB2-amplified breast cancer cell lines leads to a c-Src-dependent increase in PRC2 activity compared to parental cells, while loss of function of c-Src or PRC2 inhibits the growth of Lapatinib-resistant cells. Our data indicate that regulation of metabolic programs and control of PRC2 activity by c-Src may be important factors in the progression of ErbB2-driven breast cancer. These data may identify targetable vulnerabilities and suggest novel routes for combination therapy of ErbB2-amplified breast cancers.