Many factors contribute to students' academic success, and some, including first-generation (FG) college student status and academic preparation, are especially relevant in physiology programs. The purpose of this qualitative study was to examine FG college students' perceptions of academic preparedness and intended success strategies with the goal of informing program-level strategies to support FG students in similar undergraduate physiology-related programs. FG freshmen completed short surveys and reflections at the start and end of the semester. Qualitative responses from written reflections were compiled, and content was analyzed. Students were high achievers in high school; 98% expected As and Bs in college, but only 53% had achieved this by the end of the first semester. At the start of the semester, FG students reported feeling prepared academically but were hoping to improve their academic readiness skills, and academic success plans focused on organizational strategies. At the end of the semester, some thought they were as prepared as they expected, but most found they were not as academically prepared for college as they had expected. Several minor themes were identified as areas to address with future cohorts. This study proposes several potential avenues by which to support FG freshmen's academic success in similar physiology programs, including early identification of at-risk students, setting realistic expectations, educating students early and often about evidence-based strategies, and developing academic recovery strategies as needed.