Interfaces can influence the mechanical properties of metallic multilayers, even between different combinations of face-centered cubic (FCC)/body-centered cubic (BCC) constituents, as reported from many experiments. Recent literature has shown promise for fracture being delayed or even stopped at these interfaces. However, no studies have investigated the influence of their constituents on the subsequent mechanisms of fracture leading to failure. We performed in situ microfracture bending tests of the notched clamped beams made from physical vapor deposited Cu/Nb and Al/Nb multilayers. A catastrophic, linear elastic, brittle fracture was observed for the Cu/Nb beams, whereas a more delayed fracture with a gradual crack propagation was observed for the Al/Nb beams. These observations reveal differences in mechanisms because of the FCC element, interface/boundary blocking of dislocation motion, and effect of grain boundaries in the multilayers. Through this study, FCC/BCC metallic multilayers can be designed with enhanced fracture resistance and mechanical strength.