In F-theory, U(1) gauge symmetries are encoded in rational sections, which generate the Mordell-Weil group of the elliptic fibration of the compactification space. Recently the possible U(1) charges for global SU(5) F-theory GUTs with smooth rational sections were classified [1]. In this paper we utilize this classification to probe global F-theory models for their phenomenological viability. After imposing an exotic-free MSSM spectrum, anomaly cancellation (related to hypercharge flux GUT breaking in the presence of U(1) gauge symmetries), absence of dimension four and five proton decay operators and other R-parity violating couplings, and the presence of at least the third generation top Yukawa coupling, we generate the remaining quark and lepton Yukawa textures by a Froggatt-Nielsen mechanism. In this process we require that the dangerous couplings are forbidden at leading order, and when re-generated by singlet vevs, lie within the experimental bounds. We scan over all possible configurations, and show that only a small class of U(1) charge assignments and matter distributions satisfy all the requirements. The solutions give rise to the exact MSSM spectrum with realistic quark and lepton Yukawa textures, which are consistent with the CKM and PMNS mixing matrices. We also discuss the geometric realization of these models, and provide pointers to the class of elliptic fibrations with good phenomenological properties.