Cells in the body are exposed to dynamic external and internal environments, many of which cause cell damage. The cell’s response to this damage, broadly called the stress response, is meant to promote survival and repair or remove damage. However, not all damage can be repaired, and sometimes, even worse, the stress response can overtax the system itself, further aggravating homeostasis and leading to its loss. Aging phenotypes are considered a manifestation of accumulated cellular damage and defective repair. This is particularly apparent in the primary cell type of the articular joint, the articular chondrocytes. Articular chondrocytes are constantly facing the challenge of stressors, including mechanical overloading, oxidation, DNA damage, proteostatic stress, and metabolic imbalance. The consequence of the accumulation of stress on articular chondrocytes is aberrant mitogenesis and differentiation, defective extracellular matrix production and turnover, cellular senescence, and cell death. The most severe form of stress-induced chondrocyte dysfunction in the joints is osteoarthritis (OA). Here, we summarize studies on the cellular effects of stressors on articular chondrocytes and demonstrate that the molecular effectors of the stress pathways connect to amplify articular joint dysfunction and OA development.