Luffy's most significant and earliest-revealed weakness stems directly from his consumption of a Devil Fruit: his complete vulnerability to seawater.
Seawater: The Devil Fruit User's Bane
As a Devil Fruit user, Monkey D. Luffy shares a universal limitation with all others who have gained powers from these mystical fruits. Contact with seawater renders him utterly helpless, instantly draining his strength and making him unable to swim or utilize his Rubber-Rubber abilities. This effect means that prolonged immersion in the sea would lead to him drowning, as his body becomes too weak to move, effectively sapping away all his power and physical capability. This fundamental weakness makes large bodies of water, particularly the ocean, one of the greatest threats to his survival and effectiveness in combat.
