A numerical and experimental study of the anisotropy of the magnetoelectric (ME) response in tri-layered composites based on single-crystalline piezoelectrics has been carried out. Quasi-static and resonant direct ME measurements were performed on Metglas/Piezoelectric/Metglas tri-layered structures featuring thin foils of the magnetostrictive Metglas alloy and differently oriented piezocrystals of LiNbO3 (LNO) and GaPO4 (GPO). The transversal ME effects were found to be strongly dependent on the direction of the applied in-plane magnetic bias fields as well as the orientation of the crystals. Multiple peaks of the ME response were observed corresponding to different contour resonance modes of the piezocrystals. The largest ME coefficient of up to 249 V/(cm·Oe) was observed for a composite with a 41 °Y-cut LNO crystal at 323.1 kHz. In summary, we have shown that crystalline lead-free LNO and GPO can exhibit relatively large anisotropic ME effects in multilayers. The relations between the directional ME coupling and the material constants of the differently oriented piezocrystals were pinpointed. The precise control of this orientation should therefore allow one to engineer almost any desired quasi-static and resonant ME anisotropic properties for any specific application.