Piezoelectric energy harvesters represent a viable and well-proven solution to convert ambient vibrations into useful electric power within a number of modern life applications. Whilst a large amount of studies has focused on improving power output from these devices, relatively little research has been directed to investigate how these devices degrade over time and the effect this has on long-term power generation. This paper, therefore, aims to experimentally investigate how piezoelectric vibration energy harvesters degrade during long-term operation in realistic harvesting conditions. The harvesters tested are unimorph cantilevers based on three of the most commonly used piezoelectric options: polyvinylidene fluoride (PVDF), Macro Fiber Composite (MFC), and Quick Pack (QP). Testing was carried out under single-frequency excitation (10–40 Hz) of 1g amplitude for three million vibration cycles. Our results show that the natural frequency and the optimum load resistance of the harvesters may vary during prolonged operation. Importantly, a larger cumulative variation in natural frequency and optimum load resistance yields a larger variation in power output, thereby linking the variation in power to the variation of the mechanical and/or electrical properties of the harvesters. Comparing the average power values over the testing period we found that increasing the tip mass does not necessarily improve the average power output, suggesting that a larger tip mass may exacerbate the degradation of the mechanical and/or electrical properties of the harvester. This was particularly evident for the stiffest QP harvesters which showed the highest signs of power degradation; nevertheless, QP harvesters still managed to demonstrate the highest power density values. When cost consideration is taken into account in the assessment, PVDF harvesters managed to demonstrate the highest power density to cost ratio.