Moderate-to-vigorous intensity physical activity (MVPA) reduces breast cancer risk, although the effects of MVPA in different settings across the life course and how they may differ by menopausal status are unclear. This gap was addressed using data from a case-control study of 1,110 incident breast cancer cases and 1,172 cancer-free controls, frequency matched by age, from Vancouver and Kingston, Canada. In Vancouver, cases were recruited from the British Columbia Cancer Registry and controls from the Screening Mammography Program of British Columbia and in Kingston cases and controls were recruited from a breast assessment center. Lifetime leisure-time, household, and occupational MVPA energy expenditures were assessed in an open-ended questionnaire and mean weekly metabolic equivalent hours (MET-h/week) were calculated for the age periods 12-17, 18-34, 35-49, and ≥50 years and for the total lifetime. Odds ratios were estimated separately for pre- and for post-menopausal women using unconditional logistic regression. Among post-menopausal women, each of >22.9 MET-h/week of mean lifetime leisure-time MVPA (equivalent to running for 3 h) and >61.1 MET-h/week of mean lifetime household MVPA (equivalent to 24 h of moderate household work) reduced breast cancer risk by 40 %, compared to 0 MET-h/week of each. The respective ORs were 0.63 (95 % CI 0.42-0.94) and 0.58 (95 % CI 0.43-0.79). Among post-menopausal women, leisure-time MVPA after age 35 was more strongly associated with reduced breast cancer risk than MVPA in early life, while household MVPA was associated with reduced risk at all adulthood age periods. The weekly volume of leisure-time MVPA required to reduce post-menopausal breast cancer risk was consistent with amount recommended in the World Cancer Research Fund/American Institute for Cancer Research guidelines for cancer prevention.