The aim of the study was to assess the feasibility and effectiveness of aquatic-based exercise in the form of deep water running (DWR) as part of a multimodal physiotherapy programme (MMPP) for breast cancer survivors. A controlled clinical trial was conducted in 42 primary breast cancer survivors recruited from community-based Primary Care Centres. Patients in the experimental group received a MMPP incorporating DWR, 3 times a week, for an 8-week period. The control group received a leaflet containing instructions to continue with normal activities. Statistically significant improvements and intergroup effect size were found for the experimental group for Piper Fatigue Scale-Revised total score (d = 0.7, P = 0.001), as well as behavioural/severity (d = 0.6, P = 0.05), affective/meaning (d = 1.0, P = 0.001) and sensory (d = 0.3, P = 0.03) domains. Statistically significant differences between the experimental and control groups were also found for general health (d = 0.5, P < 0.05) and quality of life (d = 1.3, P < 0.05). All participants attended over 80% of sessions, with no major adverse events reported. The results of this study suggest MMPP incorporating DWR decreases cancer-related fatigue and improves general health and quality of life in breast cancer survivors. Further, the high level of adherence and lack of adverse events indicate such a programme is safe and feasible.