BACKGROUND: The COVID-19 pandemic has disrupted human societies around the world. This public health emergency was followed by a significant loss of human life; the ensuing social restrictions led to loss of employment, lack of interactions, and burgeoning psychological distress. As physical distancing regulations were introduced to manage outbreaks, individuals, groups, and communities engaged extensively on social media to express their thoughts and emotions. This internet-mediated communication of self-reported information encapsulates the emotional health and mental well-being of all individuals impacted by the pandemic. OBJECTIVE: This research aims to investigate the human emotions related to the COVID-19 pandemic expressed on social media over time, using an artificial intelligence (AI) framework. METHODS: Our study explores emotion classifications, intensities, transitions, and profiles, as well as alignment to key themes and topics, across the four stages of the pandemic: declaration of a global health crisis (ie, prepandemic), the first lockdown, easing of restrictions, and the second lockdown. This study employs an AI framework comprised of natural language processing, word embeddings, Markov models, and the growing self-organizing map algorithm, which are collectively used to investigate social media conversations. The investigation was carried out using 73,000 public Twitter conversations posted by users in Australia from January to September 2020. RESULTS: The outcomes of this study enabled us to analyze and visualize different emotions and related concerns that were expressed and reflected on social media during the COVID-19 pandemic, which could be used to gain insights into citizens' mental health. First, the topic analysis showed the diverse as well as common concerns people had expressed during the four stages of the pandemic. It was noted that personal-level concerns expressed on social media had escalated to broader concerns over time. Second, the emotion intensity and emotion state transitions showed that fear and sadness emotions were more prominently expressed at first; however, emotions transitioned into anger and disgust over time. Negative emotions, except for sadness, were significantly higher (P<.05) in the second lockdown, showing increased frustration. Temporal emotion analysis was conducted by modeling the emotion state changes across the four stages of the pandemic, which demonstrated how different emotions emerged and shifted over time. Third, the concerns expressed by social media users were categorized into profiles, where differences could be seen between the first and second lockdown profiles. CONCLUSIONS: This study showed that the diverse emotions and concerns that were expressed and recorded on social media during the COVID-19 pandemic reflected the mental health of the general public. While this study established the use of social media to discover informed insights during a time when physical communication was impossible, the outcomes could also contribute toward postpandemic recovery and understanding psychological impact via emotion changes, and they could potentially inform health care decision making. This study exploited AI and social media to enhance our understanding of human behaviors in global emergencies, which could lead to improved planning and policy making for future crises.