Due to the inherently low adhesive strength and structural integrity of polymer thermal interface materials (TIMs), they present a likely point of failure when succumbed to thermomechanical stresses in electronics packaging. Herein, we present a methodology to quantify TIM degradation through an accelerated and repeatable mechanical cycling technique. The testing apparatus incorporated a steady-state thermal conductivity measurement system, consistent with ASTM 5470-06, with added displacement actuation and force sensing to provide controlled cyclic loading between −20 N and 20 N. Additionally, a novel optical technique was utilized to observe void formation, pump-out, and dry-out behavior during cycling, in order to correlate the thermal performance with physical behaviors of different TIMs under cyclic stress. Of the two different pastes analyzed, cyclic testing was found to degrade the thermal performance of the less viscous TIM by increasing its interfacial resistance. Optical qualitative measurements revealed the breakdown of the TIM structure at the interface, which indicated the formation of voids due to TIM degradation. Applying this testing method for future TIM development could help in optimizing TIM structure for particular package applications.