Background: The COVID-19 pandemic has impacted the entire world in unprecedented ways. However, populations that have had a history of marginalization have experienced a more profound impact. One such group is Latinx families of children with intellectual and developmental disabilities (IDD) in the Unites States. Methods: In this study, we used a mixed methods approach to explore the impact of the pandemic on the mental health and well-being of Latinx caregivers of children with IDD. Results: Specifically, we (1) identified which social determinants of health are correlated with maternal caregivers perceived general health, mental health, and well-being; (2) explored the impact of the pandemic on families’ overall eating and physical activity routines; and (3) identified emergent themes from caregivers’ experiences during the pandemic. Thirty-seven Latinx caregivers participated in three interviews in which several validated instruments were administered. The results indicated that perceived social support, annual family income, food security, and receipt of financial benefits were correlated with fewer depressive symptoms. Annual family income was also significantly correlated with perceived general health. Most caregivers reported that the pandemic had placed a strain on their economic situation; increased their isolation; and disrupted their child’s therapeutic supports, online education, eating routines, and engagement in physical activity. Meanwhile, some caregivers reported positive changes as a result of the pandemic. Conclusions: Implications for future research and practice are discussed.