Jonathan Drake, while attending his brother's funeral, is shocked to find the head of the deceased is missing. When his brother's skull shows up later in a locked cabinet, Drake realizes an ancient curse placed upon his grandfather by a tribe of South American Jivaro Indians is still in effect and that he himself is the probable next victim.

While guiding a hunting party of clueless European aristocrats, cowboy Bosky Fulton leads them into hostile Apache territory. Becoming separated from the group, Countess Irina Lazaar experiences the first run-in with an Apache, which results in the tracker Shalako coming to her rescue. Despite Shalako's warning to leave the area immediately, the pampered foreigners fail to take him seriously, leaving them in grave danger.