In the context of the 2HDM, and assuming that neutrinos acquire masses via the Weinberg operator, we perform a systematic analysis to determine the minimal quark and lepton flavor patterns, compatible with masses, mixing and CP violation data, realizable by Abelian symmetries. We determine four minimal models for quarks, where the number of independent parameters matches the number of observables. For the lepton sector, three minimal predictive models are identified. Namely, we find scenarios with a preference for the upper/lower octant of the θ23 atmospheric mixing angle, that exhibit lower bounds on the lightest neutrino masses currently probed by cosmology and testable at future neutrinoless double beta decay experiments, even for a normally ordered neutrino masses. We investigate the phenomenology of each model taking into account all relevant theoretical, electroweak precision observables, scalar sector constraints, as well as stringent quark flavor processes such as B¯→Xsγ, Bs→μ−μ+ and meson oscillations, and the charged lepton flavor-violating decays eα−→eβ−eγ+eδ− and eα→eβγ. We show that, in some cases, Abelian flavor symmetries provide a natural framework to suppress flavor-changing neutral couplings and lead to scenarios featuring heavy neutral/charged scalar masses below the TeV scale within the reach of current experiments. Published by the American Physical Society 2024