Accumulating research suggests that stressful life events, especially those that threaten close intimate bonds, are associated with an increased risk of dementia. Grieving the loss of a spouse, whether in the form of caregiving or after the death, ranks among 'life's most significant stressors’, evoking intense psychological and physiological distress. Despite numerous studies reporting elevated dementia risk or poorer cognition among spousal caregivers and widow(er)s compared to controls, no review has summarized findings across cognitive outcomes (i.e., dementia incidence, cognitive impairment rates, cognitive performance) or proposed a theoretical model for understanding the links between partner loss and abnormal cognitive decline. The current systematic review summarizes findings across 64 empirical studies. Overall, both cross-sectional and longitudinal studies revealed an adverse association between partner loss and cognitive outcomes. In turn, we propose a biopsychosocial model of cognitive decline that explains how caregiving and bereavement may position some to develop cognitive impairment or Alzheimer's disease and related dementias. More longitudinal studies that focus on the biopsychosocial context of caregivers and widow(er)s are needed.