The present study examined (1) intraindividual changes in the frequency of electronic nicotine delivery systems (ENDS) use across young adulthood, 18 to 30 years old, and (2) if depressive symptoms and sensation-seeking tendencies, independently and in interaction with one another, were associated with these changes. Data were from a longitudinal study of students recruited from 24 Texas colleges and followed across six waves from fall 2015 to spring 2019. Participants (n = 1298; 36.3% non-Hispanic white, 56.3% women) were 18 to 26 years old in fall 2015 and all reported past 30-day ENDS use on at least one wave. We used growth curve modeling for an accelerated longitudinal design to examine if ENDS use frequency changed with increasing age and if depressive symptoms and sensation seeking, independently and in interaction with one another, were associated with these changes. Results showed that ENDS use frequency increased with increasing age. Depressive symptoms and sensation seeking were not independently associated with more frequent ENDS use or an accelerated increase in ENDS use frequency across increasing age. However, a significant two-way interaction indicated that young adults with elevated depressive symptoms used ENDS more frequently, but only when they had higher levels of sensation seeking. Findings indicate that young adults with depressive symptoms are a heterogeneous population and that those with high levels of sensation-seeking tendencies are at elevated risk for more frequent ENDS use. Interventions for young adults high in both sensation-seeking and depressive symptoms may help prevent and decrease ENDS use.