Coral reefs provide environmental goods and services that support biodiversity and people but face diverse threats. To assess the human factors that might be influencing the status of Cuban coral reefs, we collected and analyzed data from three sources: observations made on a research cruise that circumnavigated Cuba’s waters, expert knowledge, and updated published information. Our results show that small-scale fisheries are predominant among human factors influencing Cuban coral reefs, with more than 97% of the fishing incidents detected in situ during the expedition. Many Cuban reefs are heavily fished, have low levels of contamination, and enjoy high legal protection but experience inadequate enforcement. Tourism occurs on many reefs but could be sustainably increased based on its role in supporting enforcement and compliance and reducing fishing pressure. Densities of marine debris were generally lower in Cuban waters than other Caribbean locations and even lower within protected areas. Many human factors are likely acting synergistically, making management a challenge. This is the first at-sea comprehensive visual survey of human factors in Cuban waters and evaluation of marine debris on Cuba’s reefs, establishing a baseline for future assessments. These findings highlight potential human impacts that must be addressed to safeguard the health of Cuba’s marine ecosystem.