Multiple partner fertility (or MPF) is a pervasive and durable component of American family life, with 1 in 5 women—and nearly 1 in 4 mothers—having children with two or more men during their lifetime; and, these women tend to fare worse than their single partner fertility counterparts in terms of lower mental and physical health and higher rates of depression. Further, MPF households are more likely than other households to be characterized by single parenthood, poverty, and low parental education and underemployment. Using a life course perspective and social stress theories as a guide, I provide evidence from the National Longitudinal Survey of Youth 1979–2006 which suggests that MPF represents a theoretically important constellation of events that have the potential to disrupt day-to-day life, change family roles, create ambiguity, and introduce chronic stressors into the home that are associated with significant declines in maternal well being over the long-term. This project also considers whether having multiple partner fertility makes women more vulnerable to stressful life experiences. Overall, there was little support of differential vulnerability hypothesis, however, there were several significant interactions which provided surprising results. For example, as the number of residential partners increased, women with single partner fertility saw larger declines in mental health than women with multiple partner fertility. Likewise, single partner fertility mothers were more likely than multiple partner fertility mothers to see declines in physical health as time in poverty increased, and saw fewer gains in mental health and depression as time employed increased. Similarly, among MPF women, Hispanic and African American mothers had higher levels of physical health, mental health, and depression than White mothers. Although these findings were unexpected, they were not without precedent in other literatures, and they provide an important new framework for understanding serial parents who face cumulative disadvantages.