Studies of plant invasions have primarily focused on effects within shared habitats of native and invasive species. However, secondary compounds produced by terrestrial invasive plants can cross terrestrial-aquatic boundaries via senesced leaves, leading to altered patterns of aquatic biodiversity and ecosystem functioning. Impacts of phenolic compounds from senesced leaves have been characterized among relatively lower trophic groups, but effects on keystone species, such as apex predators, should have disproportionately larger effects on aquatic food webs. Using a widespread invasive species (Amur Honeysuckle, Lonicera maackii), we employed experimental mesocosms to examine effects of honeysuckle leaf litter addition on survival of apex predators (larval spotted salamanders, Ambystoma maculatum), their zooplankton and macroinvertebrate prey, indicators of primary productivity and decomposition, and abiotic variables influenced by phenolic compounds. Despite previous laboratory observations suggesting A. maculatum might exhibit resistance to L. maackii leachates, we observed near complete loss of both A. maculatum and benthic macroinvertebrates in experimental mesocosms, while zooplankton abundance was unaffected. Mortality was likely associated with precipitous declines in dissolved oxygen following rapid decomposition of L. maackii leaves, and these conditions facilitated nearly 15-fold increases in larval mosquito abundance. Our results highlight how experimental venue and methodology may alter outcomes of investigations involving senesced leaves of invasive plants. Losses of amphibian predators under quasi-natural invasion conditions indicate important influences on terrestrial-aquatic nutrient exchange, and we highlight phenological patterns of leaf senescence and breeding by aquatic organisms as important avenues for further investigation in characterizing the consequences of plant invasions.