Objective: Back pain causes greater disability worldwide than any other condition, with women more likely to experience back pain than men. Our aim was to identify modifiable risk factors for back pain in middle-aged women. Methods: Women born between 1946 and 1951 were randomly selected from the national health insurance scheme database to participate in The Australian Longitudinal Study on Women's Health. Self-reported data on back pain in the last 12 months, and on weight, physical activity, and other sociodemographic factors, were collected in 1998, 2001, 2004, 2007, 2010, and 2013. In 1998, a total of 12,338 women completed the survey and 10,011 (74%) completed the 2013 survey. Results: At baseline, median (range) age was 49.5 years (44.6–53.5 years), and 54% reported back pain. In multivariate analysis, baseline weight and depression were positive predictors of back pain over each 3-year survey interval and over the following 15 years, whereas participation in vigorous physical activity was protective. The effects of weight on back pain were most marked in women with a body mass index of ≥25 kg/m2. Conclusion: Back pain is common in middle-aged women. Increased weight, weight gain, and depression were independent predictors of back pain over 15 years, whereas participation in vigorous physical activity was protective. Targeting these lifestyle factors is an important area for future research on reducing the burden of back pain in middle-aged women.