The most important driver of the continuing decline in lion populations is habitat loss and conversion of safe space, which leads to subpopulations becoming small and isolated. Compounding this is human–lion conflict, which results in the indiscriminate killing of lions, often as a retaliatory or pre-emptive measure to protect livestock and human life. Lions are particularly vulnerable to being poisoned by carcasses put out to eliminate predators due to their scavenging behavior.

Prey base depletion is another significant and intensifying driver of decline, linked primarily to poaching and the unsustainable, often commercialized, bushmeat trade, which reduces the carrying capacity of lion habitat. An emerging, significant threat is the targeted poaching for bones and other body parts (such as skins, claws, and teeth) for use in traditional medicine within Africa and Asia; this threat is escalating and can cause significant population declines, notably observed in Mozambique.

Additionally, bycatch in snares set for bushmeat is widespread and frequently entraps non-target large carnivores like lions, posing a threat that can cause severe local population declines. Finally, violent extremism, civil unrest, and warfare are escalating threats in several parts of Africa, which severely undermine conservation efforts by disrupting park management, leading to increased illegal activities, and causing local extinctions. All these threats are exacerbated by a persistent lack of sufficient funding to manage protected areas effectively.