In 2018, researchers declared a “graduate student mental health crisis” after finding that graduate students were significantly more likely to report experiencing depression and anxiety compared to their peers in the general population. Calls to create more inclusive graduate programs for students with anxiety and depression followed. However, little research has examined what aspects of graduate school can alleviate and exacerbate graduate student symptoms of anxiety and depression. We conducted a sequential mixed-methods study to address this gap in the literature. We began by conducting interview studies of graduate students with depression (n = 50) and graduate students with anxiety (n = 33) to identify what aspects of graduate research and teaching alleviate and exacerbate students’ symptoms of depression and anxiety. We used the data from these studies to inform a survey study of 2700 science PhD and Master’s students. We found that depression and anxiety disproportionately impact women, financially unstable students, and LGBTQ+ individuals, and that students who identify as having anxiety and/or depression are disproportionately likely to seriously consider leaving their graduate program. We identified aspects of research and teaching that can alleviate and exacerbate student depression and anxiety, providing novel targets to bolster grad student mental health and create more inclusive science graduate programs.