Al-Ti-B based master alloys have been widely used for grain refining of Al-alloys in industry for many decades. However, the effectiveness of such grain refiners is severely compromised when a few hundred ppm of Zr is present in the Al melt, and this phenomenon is referred to as Zr poisoning in the literature. So far the exact mechanisms for Zr poisoning are not clear albeit significant research effort on the subject in the last few decades. In this work we investigated the mechanism for Zr poisoning through extensive examinations of the Al/TiB2 interface using the state-of-the-art electron microscopy and ab initio molecular dynamics simulations. We found that the presence of Zr in Al melts leads to (i) the dissolution of the Al3Ti 2-dimensional compound (2DC) formed on the (0 0 0 1) TiB2 surface during the grain refiner production process; and (ii) the formation of an atomic monolayer of Ti2Zr 2DC on the (0 0 0 1) TiB2 surface, which replaces the original Ti-terminated TiB2 basal surface. This monolayer of Ti2Zr not only has large lattice misfit (4.2%) with α-Al, but also is atomically rough, rendering the TiB2 particles impotent for heterogeneous nucleation of α-Al. This work, in combination of our previous work, demonstrates that heterogeneous nucleation can be effectively manipulated, either enhanced or impeded, by chemical segregation of selected alloying/impurity elements at the liquid/substrate interface. (a, b) High resolution STEM HAADF images showing an atomic monolayer of Ti2Zr 2-dimensional compound (2DC) on (0 0 0 1) surface of TiB2 being viewed along (a) 1 1 -2 0TiB2 and (b) 1 0 -1 0TiB2 direction respectively, and (c) 3D construction of the Ti2Zr 2DC on top of TiB2. Display omitted