The early 2020s witnessed an unprecedented overlap of multiple global crises. This longitudinal study examined the compounded effects of multiple intersecting global crises on mental health outcomes in a representative cohort of East German adults. We investigated how perceived threats (PT) from climate change (PT-CLC), COVID-19 (PT-COV), the Russia–Ukraine War (PT-RUW), and rising costs of living (PT-RCL) will impact various aspects of mental health from 2021 to 2022. This research question addresses whether these crises exacerbate mental health issues and how their effects differ across various mental health outcomes. Methods: We conducted a longitudinal study with 319 participants (mean age 49.9 years, 54.5% female) from the Saxony Longitudinal Study. Data were collected in two waves: March–July 2021 and September–December 2022. We used linear mixed-effects models to analyze both unadjusted group trends and adjusted individual-level effects on physical complaints, mental distress, sleep problems, life satisfaction, and self-rated health. Results: Unadjusted analyses revealed significant increases in mental distress and sleep problems over time, whereas physical complaints, life satisfaction, and self-rated health remained stable at the group level. Adjusted analyses showed that higher PT-RCL and PT-COV were significantly associated with increased physical complaints, mental distress, sleep problems, and decreased life satisfaction, even when group-level changes were not significant. Conclusions: This study highlights the complex impact of intersecting global crises on mental health, emphasizing the importance of considering both population-level trends and individual perceptions. The findings suggest that economic and pandemic-related stressors have more immediate effects on mental health outcomes compared to more distant threats, such as climate change or geopolitical conflicts.