DNA unzipping by nanopore translocation has implications in diverse contexts, from polymer physics to single-molecule manipulation to DNA–enzyme interactions in biological systems. Here we use molecular dynamics simulations and a coarse-grained model of DNA to address the nanopore unzipping of DNA filaments that are knotted. This previously unaddressed problem is motivated by the fact that DNA knots inevitably occur in isolated equilibrated filaments and in vivo. We study how different types of tight knots in the DNA segment just outside the pore impact unzipping at different driving forces. We establish three main results. First, knots do not significantly affect the unzipping process at low forces. However, knotted DNAs unzip more slowly and heterogeneously than unknotted ones at high forces. Finally, we observe that the microscopic origin of the hindrance typically involves two concurrent causes: the topological friction of the DNA chain sliding along its knotted contour and the additional friction originating from the entanglement with the newly unzipped DNA. The results reveal a previously unsuspected complexity of the interplay of DNA topology and unzipping, which should be relevant for interpreting nanopore-based single-molecule unzipping experiments and improving the modeling of DNA transactions in vivo.