Energy densities (ED, mJ/mm) quantify mechanical work imposed on articular cartilages during function. This cross-sectional study examined differences in temporomandibular joint (TMJ) ED during asymmetric versus symmetric jaw closing in healthy females versus males. ED component variables were tested for differences between and within sexes for two types of jaw closing. Seventeen female and 17 male subjects gave informed consent to participate. Diagnostic criteria for temporomandibular disorders and images (magnetic resonance (MR), computed tomography) were used to confirm healthy TMJ status. Numerical modelling predicted TMJ loads (F) consequent to unilateral canine biting. Dynamic stereometry combined MR imaging and jaw-tracking data to measure ED component variables during 10 trials of each type of jaw closing in each subject's TMJs. These data were then used to calculate TMJ ED during jaw closing asymmetrically and symmetrically. Paired and Student's t tests assessed ED between jaw closing movements and sexes, respectively. Multivariate data analyses assessed ED component variable differences between jaw closing movements and sexes (α = 0.05). Contralateral TMJ ED were 3.6-fold and significantly larger (P < .0001) during asymmetric versus symmetric jaw closing, due to significantly larger (P ≤ .001) distances of TMJ stress-field translation in asymmetric versus symmetric movement. During asymmetric jaw closing, contralateral TMJ ED were twofold and significantly larger (P = .036) in females versus males, due to 1.5-fold and significantly smaller (P ≤ .010) TMJ disc cartilage volumes under stress fields in females versus males. These results suggest that in healthy individuals, asymmetric compared to symmetric jaw closure in females compared to males has higher TMJ mechanical fatigue liabilities.