Background: During 2024-2025, global emergencies triggered intense online discourse, presenting a unique opportunity to examine how cultural factors shape emotional expression and knowledge dissemination. Understanding these dynamic mechanisms is crucial for enhancing the effectiveness of digital health communication and optimizing crisis response strategies. Objective: We analyzed how cultural and linguistic contexts influence emotional expression and thematic framing in social media comments during major emergencies in 2024-2025. We uncovered cross-cultural differences in collective emotions and narrative focuses, explaining how affective stance and discourse framing jointly shape the public construction of crisis meaning. Methods: We used a cross-sectional, convergent mixed methods design. Data were collected retrospectively from X (formerly Twitter; X Corp) and Weibo (Sina Weibo) between January 1 and December 31, 2024. Using purposive sampling, we selected 5-6 representative emergency events per month based on online visibility (capped at 600 comments/event). The dataset included 19,813 comments from X and 6536 comments from Weibo. Emotions were identified using a Cross-lingual Language Model-Robustly optimized Bidirectional Encoder Representations from Transformers approach, and thematic patterns were extracted with Bidirectional Encoder Representations from Transformers Topic. Integrated Gradients was used to interpret model outputs, while clustering and network analysis were applied to visualize cross-cultural patterns. Hofstede’s cultural dimensions theory helped interpret cultural influences on discourse. This mixed computational approach enabled a detailed comparison of emotional structures and thematic discourse across linguistic communities. Results: Significant cross-platform differences were observed in emotional distribution (χ²8=8025.60; P<.001). Compared to X users, Weibo users, representing a collectivist culture, expressed concentrated negative emotions (20.37%; odds ratio [OR] 15.76, 95% CI 13.90-17.85), surprise (19.70%; OR 2.53, 95% CI 2.32-2.73), and fear (16.68%; OR 1.72, 95% CI 1.58-1.86), reflecting group-oriented anxiety and emotional contagion. In contrast, X (formerly Twitter) users in individualist contexts displayed dispersed sarcasm (43.49%; OR 55.19, 95% CI 43.95-69.21) and worry (15.30%; OR 55.27, 95% CI 34.74-87.88), indicating personalized and critical emotional styles. Topic modeling revealed dense clusters around “safety,” “pray,” and “resettlement” on Weibo, whereas X (formerly Twitter) comments emphasized decentralized themes of critique and responsibility. Semantic network analysis revealed a cohesive fear-prayer-rescue chain on Weibo and fragmented, debate-oriented interactions on X (formerly Twitter). Conclusions: Emergency discourse is not neutral but is systematically structured by cultural values that shape emotions and themes. Integrating multilingual computational and qualitative methods, we offer a replicable framework using large-scale data, moving crisis and infodemiological research beyond single-platform or survey-based approaches. Our findings advance theory-informed understanding of how cultural meaning systems translate into observable digital discourse under conditions of risk and uncertainty. They also offer practical implications for governments, public health agencies, international organizations, and digital platforms by informing culturally adaptive, platform-specific risk communication, community moderation, and crisis engagement strategies that can strengthen public trust, improve compliance with protective behaviors, and mitigate infodemic-related harms.