Affect reactivity to stress may play a role in the development of internalizing symptoms during the college transition, a critical developmental juncture for Latinx adolescents, the largest ethnic minority group on college campuses. This study examined whether affect reactivity during high school is associated with internalizing symptoms in college and explored two potential protective factors, perceived family and peer support. Participants were 209 Latinx adolescents (Mage = 18.10; 64.4% female) who completed standard surveys and four diary assessments per day over 7 days (N > 4,500 momentary observations). First, to measure affect reactivity, we assessed whether perceived stress was associated with negative affect at the momentary level during high school (senior year). Second, we tested whether affect reactivity predicted internalizing symptoms during the first year of college. Third, we tested whether perceived family or peer support buffered the negative consequences of affect reactivity. Results indicated statistically significant within- and between-person associations between stress and negative affect. Moreover, affect reactivity significantly predicted depressive, but not anxiety, symptoms. Buffering was found for family, but not peer, support. Findings extend previous research by detecting associations between momentary affect reactivity and internalizing symptoms during a sociocultural shift in Latinx adolescents’ lives and have implications for culturally appropriate programs to prevent depressive symptoms.