Multimorbidity is a growing public health problem and is more common in women than men. However, little is known about multimorbidity trajectories, in terms of the accumulation of disease over time, or about the determinants of these trajectories. We sought to identify lifestyle and socioeconomic factors related to multimorbidity trajectories in mid-aged women. Participants were from the Australian Longitudinal Study on Women's Health, a nationally representative population-based study. We included 4865 women born 1946–51, without chronic disease in 1998, followed triennially for 12 years. We used latent class growth analysis to identify 9-year multimorbidity trajectories and multinomial regression to calculate relative risk ratios (RRRs) for associations between baseline lifestyle and socioeconomic factors and trajectories. We identified five multimorbidity trajectories: ‘no morbidity, constant’; ‘low morbidity, constant’; ‘moderate morbidity, constant’; ‘no morbidity, increasing’; and ‘low morbidity, increasing’. Overweight and obesity were associated with an increased risk of the ‘no morbidity, increasing’ (RRR 1.70, 95% CI 1.16 to 2.50 and 2.69, 95% CI 1.69 to 4.28, respectively) and the ‘low morbidity, increasing’ (RRR 2.57, 95% CI 1.56 to 4.24 and 4.28, 95% CI 2.41 to 7.60, respectively) trajectories, as compared to the ‘no morbidity, constant’ group. Low education and difficulty managing on income were also associated with trajectories of poorer health. Among mid-aged women, overweight/obesity and lower socioeconomic status are major risk factors for trajectories characterised by accumulation of chronic disease. These highlight key target areas for preventive approaches aimed at reducing the risk of accumulation of morbidities in mid-aged women.