AbstractCompared to the general population, mental health difficulties are commonly reported in autistic adults. However, the ways in which coping strategies are associated with mental health and well‐being in this population remain unknown. Further, we do not know if, and if so, how these associations might differ to that of non‐autistic adults. In this study, we hypothesized that in both our autistic (N = 255) and non‐autistic (N = 165) adult samples, disengagement coping strategies (e.g., denial) would relate to poorer mental health and well‐being, while engagement coping strategies (e.g., problem solving) would relate to better mental health and well‐being. Regression analyses revealed that higher use of disengagement coping strategies was significantly associated with higher levels of anxiety and depression, and lower levels of well‐being in both samples. In contrast, increased use of engagement coping strategies was associated with better well‐being, but only in the autistic sample. Our results contribute to the characterization of negative and positive mental health outcomes in autistic adults from a coping perspective, with potential to offer novel information regarding coping strategies to consider when addressing support options for mental health difficulties in the autistic adult population.Lay SummaryMental health conditions (such as anxiety and depression) and poor well‐being are commonly reported in autistic adults. Research suggests that how one copes with stress is associated with one's mental health and well‐being. However, we have little information about how coping strategies relate to the mental health of autistic adults, and whether this might be different in non‐autistic adults. In this study, we examined the relationship between coping strategies and mental health in a large group of autistic individuals aged 15–80 years. We then compared this with similar aged non‐autistic individuals. We found that in both the autistic and non‐autistic individuals, using more disengagement coping strategies (such as being in denial, blaming oneself) was related to poorer mental health and well‐being. Additionally, using more engagement coping strategies (such as problem solving, acceptance) was related to better mental health and well‐being, but only in the autistic individuals. These results can help inform support services, as they highlight the coping strategies that may need to be focused on (i.e., developing engagement coping strategies and reducing disengagement coping strategies) in order to better support the mental health of autistic individuals.