Sharks, as top order predators, provide a guidance on how contaminants such as mercury bioaccumulate in marine environments. This study assessed the bioaccumulation of mercury (total mercury, THg) in the muscle, liver, red blood cells (RBC), and plasma of pelagic and bigeye thresher sharks (Alopias pelagicus and A. superciliosus) from eastern tropical Pacific. Additionally, the concentration of methylmercury (MeHg) in muscle was also determined to assess risks for human consumption. For both species, muscle THg concentrations (4.05 ± 2.15 and 4.12 ± 1.84 μg g−1 dry weight for pelagic and bigeye thresher shark) were higher than that in other tissues. THg concentrations for all tissues were significantly correlated with precaudal length, with higher accumulation rates after maturity in pelagic than bigeye thresher sharks, suggesting an associated dietary shift at maturation. Correlations among tissues in both species suggested similar transportation and distribution patterns in internal tissues. The δ13C values in muscle, RBC and plasma suggested that habitat shifts influenced Hg accumulation, whereas trophic position, estimated by δ15N values, had limited effects on patterns of Hg bioaccumulation. Diet shifts towards prey more cephalopods that content higher Hg than small fishes (large fishes: 1.77 μg g−1; cephalopods: 0.66 μg g−1 and small fishes 0.48 μg g−1, dry weight) increased Hg accumulation rates in adult pelagic thresher sharks. Concentrations of MeHg in the muscle of both thresher shark (3.42 ± 1.68 μg g−1 in A. pelagicus and 3.78 ± 2.13 μg g−1 in A. superciliosus) exceeded the recommended levels for human consumption. This research provides insight into the factors influencing mercury bioaccumulation in thresher sharks, which are essential for the management and conservation of these species.