Interpreting ecological dynamics is challenging when observed patterns are not aligned with presumed models. Investigating possible sources of uncertainty is critical to understand the underlying system and ultimately inform management decisions. In this study, we used simulation to investigate the hypothesis that observed inconsistencies in Great Lakes lake trout (Salvelinus namaycush) and sea lamprey (Petromyzon marinus) predator-prey dynamics were caused by measurement error in the abundance and predation metrics. When lake trout abundances increase and sea lamprey abundances decrease, predation rates are expected to decline (and vice versa). Occasionally predation rates do not change as expected, leading to an inconsistency in expected predator-prey dynamics. We used a Type II functional response model to align lake trout relative abundance, adult sea lamprey abundance, and sea lamprey marking rates of lake trout in each Great Lake. Then we added measurement error to each of the simulated metrics to see how it contributed to observed inconsistencies in the marking rates. The simulated inconsistency rate was far less than the observed inconsistency rate in Lakes Superior and Erie, indicating that measurement error was not primarily responsible for the misalignment of metrics, contrary to our hypothesis. Rather than ignoring these inconsistencies as unfortunate consequences of imperfect assessments, we recommend that future inconsistencies be scrutinized for possible mechanistic explanations. We suspect that predator-prey dynamics are being influenced by spatially structured within-lake components and the presence of alternative hosts, neither of which were accounted for in the functional response model we used.