The investigation of fatigue failure in polymeric materials subjected to cyclic loading holds significant importance across diverse engineering applications. Numerous variables influence material behavior, encompassing material-related factors such as composition, molecular weight, orientation, and additives, as well as external factors like applied stress magnitude (stress amplitude, dynamic stress frequency and mean stress), and operating temperature. This paper presents an experimental exploration into the impact of loading parameters—mean stress, stress amplitude, and dynamic stress frequency—on the failure modes of two thermoplastic materials: high-density polyethylene (HDPE) and polyvinyl chloride (PVC). The study begins with an assessment of the mechanical and physical properties of the materials, followed by the design and manufacturing of a specialized uniaxial fatigue test rig. Tensile–tensile fatigue tests incorporating positive mean stress are conducted, evaluating the influence of altering stress amplitude and frequency on fatigue life and failure mode. The outcomes reveal that HDPE primarily experiences thermal and creep failure modes, with a lack of observed fatigue failure. Conversely, PVC specimens manifest three distinct failure modes: ductile, creep, and fatigue, with the type of failure contingent upon loading parameters. These findings offer significant insights into the various fatigue failure modes and contribute to an enhanced comprehension of the intricate interplay between loading dynamics and failure modes in polymeric materials.