Submarine slope failures pose hazards to coastal communities through their ability to damage seafloor infrastructure and generate tsunamis. Submarine slope failures occur along continental margins worldwide, yet our understanding of submarine slope failure evolution and tsunamigenic potential is limited. Overpressure has been a proposed mechanism for initiating and preconditioning for slope failures, but understanding of its role in slope failures is limited. In this study, we investigate overpressure-induced slope failures with different sediment compositions and properties common in the marine environment. Overpressure required for slope failure and failure behavior were investigated in relation to sediment permeability and cohesion. We investigated failures in benchtop flume experiments using mixtures of fine-grained quartz sand and cohesive smectite clay or fine-grained quartz sand and non-cohesive clay-sized quartz. In high-permeability, sand-rich systems (0–5 wt% smectite), overpressure required to induce failure directly related to smectite content (R2 of 0.89). At smectite concentrations of 25 wt% or greater, normalized overpressure (λ*) required to induce slope failure remained constant at λ* = 1.52 ± 0.55. Failure behavior also changed at 25% smectite. In sand-rich systems, a single failure event occurred even with sustained or increased overpressure. With smectite or clay-sized quartz concentrations of 25 wt% or higher, a series of slope failures occurred. Concentrations of smectite ≥25% also produced larger and more brittle failure deformation features (e.g., tension cracks and subsurface fissures). We conclude that lower permeability systems have the potential for larger failures and cohesive sediment mixtures are necessary for producing brittle failure features (e.g., tension cracks, subsurface fissures, rafted blocks, etc.). Experiments using 25, 75, and 90 wt% smectite produced rafted sediment blocks separated from the parent slope. However, experiments did not mobilize any intact blocks downslope even with a relatively steep (19°) slope. Observed experiment failure deformation features (e.g., mud-volcanism, tension cracks, clay-enriched toe deposits, etc.) match observed phenomenon in natural marine environments. From our experiments, we interpret in the presence of low-permeability, high-cohesion sediments, overpressure can produce non-tsunamigenic submarine slope failures and precondition slopes for tsunamigenic failure. Thus, our work demonstrates the importance of sediment properties and composition in relation to the types of failures produced and additionally emphasize the need for multiple factors (e.g., excess head plus seismic shaking) to mobilize large, rafted blocks downslope which has direct impact in improving coastal hazard assessment.