The kinase-ligase pair PINK1-PRKN recognizes and selectively labels worn-out and dysfunctional mitochondria with phosphorylated ubiquitin (pS65-Ub) to facilitate their elimination via autophagy (mitophagy). Although typically transient, pS65-Ub serves as a quantitative marker of mitochondrial damage but can also remain elevated due to insufficient degradation and flux through lysosomes. In human autopsy brain, the number of pS65-Ub positive cells increases with age but is also independently associated with Lewy body (LB), neurofibrillary tangles (NFT), and senile plaque (SP) burden. However, pS65-Ub seems to accumulate in distinct morphologies depending on the respective neuropathology and affected brain region. Given the coexistence of these pathologies in dementia with Lewy bodies (DLB), we investigated levels of the mitophagy marker in the hippocampus and amygdala of 371 DLB cases and studied interactions between neuropathological measures from the same regions. Significant associations were observed between pS65‐Ub levels with age, brain weight, Braak stage, Thal phase as well as counts of LBs, NFTs, and SPs in both regions. Strong synergistic effects of LB and NFT pathologies on pS65-Ub accumulation were found in the amygdala, while only additive effects of LB and SP pathologies were observed. High resolution analyses showed that cells with LB pathology exhibited mainly smaller, granular pS65-Ub deposits, while those containing NFTs showed larger, vacuolar pS65-Ub aggregates. In summary, our study revealed complex interactions between LB, NFT, and SP pathology in DLB brains, highlighting potential different molecular mechanisms underlying α-synuclein- and tau-associated mitophagy alterations.