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Contemporary research has made clear that first-generation college students face important challenges—i.e., challenges that undercut the completion of a 4-year degree and that may vary to some extent by gender. But how and why? In this article we draw on unique longitudinal and semi-structured interviews across four years with 62 first-generation college students, highlight especially important vulnerabilities they experience, and interrogate how gendered dynamics around help-seeking might mitigate or exacerbate the obstacles they encounter. Results point to several important academic, social, and financial vulnerabilities across the college years, but also some key differences by gender. Specifically, our first-generation women respondents were more likely to explicitly recognize mental health issues and family tensions while enrolled in college. Notably, however, they were also more likely than their male counterparts to engage in help-seeking, and sooner, when challenges arise; a pattern that creates greater stability across time and boosts the odds of college completion. We elaborate on our most central findings in these regards and discuss how these rich over time accounts inform sociological literatures on mobility, inequality, gender, intersectionality, and higher education.