Thin film pyrochlores have attracted considerable attention for both their unique electronic and ferroic properties, as well as their radiation tolerance. These materials are able to accommodate radiation damage through the formation of defected fluorite and other structures. Furthermore, by substituting different cation species onto the B-site sublattice, it is possible to engineer various kinds of useful functional properties, but less is known about how such substitution in turn affects irradiation behavior. Here we describe a systematic study of defects generated in model La2Ti2-xZrxO7 single-crystal thin films that have been irradiated using 1 MeV Zr ions. We employ a combination of atomic-scale scanning transmission electron microscopy (STEM) and electron energy loss spectroscopy (EELS) to examine the local defect microstructure in these materials. Our experiments are informed by density functional theory (DFT) calculations, which offer insight into damage mechanisms and serve as inputs for novel multislice image simulations to interpret our STEM results. We show that this comprehensive characterization and modeling approach can help disentangle the complex interplay of structure, cation chemistry, and defect generation in this promising class of materials.