Background: handgrip strength (HGS) is a health-status parameter associated with multicomorbidity in the adult population. Objective: the aim of the present study was to determine the association between HGS (i.e., absolute and relative) and abdominal obesity (AO), type-2 diabetes (T2D), and hypertension (HT), as well as to determine the association between low relative HGS with the presence of multicomorbidity (i.e., the co-occurrence of two or more comorbidities together) in a Mexican population. Methodology: a cross-sectional study was carried out in 860 participants from the south of Mexico (661 women and 199 men). The age range evaluated was from 18 to 65 years. Assessments were made of sociodemographic data, clinical history, anthropometric parameters, and measurement of maximal HGS. Results: the regression models adjusted by age show that the presence of comorbidities (i.e., AO, HT and T2D) was linked negatively to HGS (i.e., absolute and relative). Moreover, in men, a low relative HGS in both hands reported an association with the presence of three simultaneous comorbidities (right, RR: 17.2, p < 0.001; left, RR: 11.92, p = 0.020). In women the same association was found (right, RR: 10.42, p < 0.001; left, RR: 9.90, p < 0.001). Conclusion: lower levels of relative HGS were linked to the presence of simultaneous comorbidities (i.e., the joint presence of AO, T2D and HT). Furthermore, HGS (i.e., absolute and relative) presented an inverse association with individual anthropometric and clinical parameters related to cardiovascular risk in the Mexican population.