Genetic background is estimated to play >50% in common obesity etiology. FTO single nucleotide polymorphisms (SNPs) are strongly associated with BMI, typically in European cohorts. We investigated the interaction of common FTO SNPs with actionable environmental factors, namely physical activity, sugar-sweetened beverages (SSB) and wine consumption, and verified FTO common SNPs predisposition to obesity in the Israeli population. Adults’ (>18 years old, n = 1720) FTO common SNPs data and lifestyle and nutrition habits questionnaires were analyzed using binary logistic regression models, adjusted for confounding variables (age, sex) assuming dominant, recessive and additive genetic models. Eighteen FTO SNPs were associated with significant increased obesity risk and interacted with physical activity (p < 0.001), wine consumption (p < 0.014) and SSB consumption (p < 0.01). Inactive rs9939609 risk-allele carriers had significantly higher obesity risk compared to their active counterparts (OR = 2.54, 95% CI 1.91−3.39 and OR = 3.77, 95% CI 2.47−5.75; p < 0.001 with 3.1 and 3.5 BMI increment for heterozygotes and homozygotes, respectively). SSB consumption (≥1 serving/day) significantly raised obesity risk and wine consumption (1−3 drinks/weekly) significantly lowered obesity risk for rs9939609 risk-allele carriers (OR = 1.54, 95% CI 1.05−2.27; p = 0.028 and OR = 0.61, 95% CI 0.47−0.79; p < 0.001, respectively). Our findings demonstrate that actionable lifestyle factors modify the common FTO obesity risk in predisposed carriers, and they have personal and public health implications.