The increasing level of anthropogenic CO2 in the atmosphere has made it imperative to investigate an efficient method for carbon sequestration. Geological carbon sequestration presents a viable path to mitigate greenhouse gas emissions by sequestering the captured CO2 deep underground in rock formations to store it permanently. Geochemistry, as the cornerstone of geological CO2 sequestration (GCS), plays an indispensable role. Therefore, it is not just timely but also urgent to undertake a comprehensive review of studies conducted in this area, articulate gaps and findings, and give directions for future research areas. This paper reviews geochemistry in terms of the sequestration of CO2 in geological formations, addressing mechanisms of trapping, challenges, and ways of mitigating challenges in trapping mechanisms; mineralization and methods of accelerating mineralization; and the interaction between rock, brine, and CO2 for the long-term containment and storage of CO2. Mixing CO2 with brine before or during injection, using microbes, selecting sedimentary reservoirs with reactive minerals, co-injection of carbonate anhydrase, and enhancing the surface area of reactive minerals are some of the mechanisms used to enhance mineral trapping in GCS applications. This review also addresses the potential challenges and opportunities associated with geological CO2 storage. Challenges include caprock integrity, understanding the lasting effects of storing CO2 on geological formations, developing reliable models for monitoring CO2–brine–rock interactions, CO2 impurities, and addressing public concerns about safety and environmental impacts. Conversely, opportunities in the sequestration of CO2 lie in the vast potential for storing CO2 in geological formations like depleted oil and gas reservoirs, saline aquifers, coal seams, and enhanced oil recovery (EOR) sites. Opportunities include improved geochemical trapping of CO2, optimized storage capacity, improved sealing integrity, managed wellbore leakage risk, and use of sealant materials to reduce leakage risk. Furthermore, the potential impact of advancements in geochemical research, understanding geochemical reactions, addressing the challenges, and leveraging the opportunities in GCS are crucial for achieving sustainable carbon mitigation and combating global warming effectively.