Social difficulties and mental health are primary behavioral health concerns in autistic young adults, perhaps especially during key life transitions such as entering college. This study evaluated how dissatisfaction with social connectedness may predict and/or maintain depression and anxiety symptoms in neurodiverse, first-semester, undergraduate students ( N = 263; n = 105 with diagnosed or suspected autism). Participation included a baseline survey battery, a brief survey completed twice per week across 12 weeks, and an endpoint survey battery. Social dissatisfaction at baseline was prospectively associated with biweekly ratings of depression symptoms, when controlling for baseline depressive symptoms. Social dissatisfaction was synchronously related to elevated sadness, anhedonia, and anxiety throughout the semester. These relationships were generally consistent across levels of baseline social motivation; however, there was one significant moderation effect—the negative relationship between baseline social satisfaction and anxiety was strongest for more socially motivated participants. More autistic traits were related to lower social satisfaction at baseline and greater mood concerns across timepoints. In contrast, greater autistic traits at baseline were related to greater satisfaction with social connectedness throughout the semester. Results support ongoing efforts to address mental health in autistic college students by highlighting the importance of social satisfaction. Lay abstract How satisfied people feel with their social connections and support is related to mental health outcomes for many different types of people. People may feel less socially connected at some times in their life—like when they start college. Feeling disconnected from others could lead to depression or anxiety. The transition to college may be especially difficult for autistic students as they are more likely to have difficulties adjusting socially. In our study, we asked 263 college students to answer questions about their emotions and social satisfaction twice per week during their first semester of college. We found that students who reported being less satisfied with their social connectedness (either at the beginning or throughout the semester) tended to express more symptoms of depression and anxiety. This relationship between social satisfaction and anxiety was even stronger for people who had a strong desire for social interaction (i.e. were more socially motivated). Students with more autistic traits tended to report more mood concerns, and they also reported being less satisfied with friendships at the beginning of the semester. This information may help to support ongoing efforts to better address mental health in autistic college students by encouraging efforts to improve social satisfaction.