Obesity is a complex multifactorial abnormality that has a well-confirmed genetic basis. However, the problem still lies in identifying the polymorphisms linked to body mass and composition. Therefore, this study aimed to analyze associations between FTO (rs9939609), FABP2 (rs1799883), and LEP (rs2167270), LEPR (rs1137101), and MC4R (rs17782313) polymorphisms and obesity-related parameters. Unrelated Caucasian males (n = 165) were recruited. All participants had similar physical activity levels. The participants were divided into two groups depending on their body mass index (BMI) and fat mass index (FMI). All samples were genotyped using real-time polymerase chain reaction (real-time PCR). When tested individually, only one statistically significant result was found. The FTO A/T polymorphism was significantly associated with FMI (p = 0.01). The chance of having increased FMI was >2-fold higher for the FTO A allele carriers (p < 0.01). Gene–gene interaction analyses showed the additional influence of all investigated genes on BMI and FMI. In summary, it was demonstrated that harboring the FTO A allele might be a risk factor for elevated fat mass. Additionally, this study confirmed that all five polymorphisms are involved in the development of common obesity in the studied population and the genetic risk of obesity is linked to the accumulation of numerous variants.