Identifying mechanisms by which degeneration alters intervertebral disc material properties and biomechanical behavior is important for clarifying back pain risk factors as well as for evaluating the efficacy of novel interventions. Our goal was to quantify and characterize degeneration-dependent changes in the disc's response to compression using a previously established murine model of disc degeneration. We performed compressive creep tests on normal and degenerated murine intervertebral discs and parameterized the biomechanical response using a previously established fluid-transport model. Using a series of biochemical and histological assays, we sought to determine how biomechanical alterations were attributable to degeneration-related changes in tissue morphology. We observed that with moderate degeneration, discs lost height (mean+/-std. dev. of 0.44+/-0.01 vs. 0.36+/-0.01 mm, p<0.0001), increased in proteoglycan content (31+/-4 vs. 43+/-2 microg/ml of extract, p<0.0002), became less stiff (2.17+/-0.66 vs. 1.56+/-0.44 MPa, p<0.053), and crept more. Model results suggested that the increased creep response was mainly due to a diminished strain-dependent nuclear swelling pressure. We also noted that the model-derived tissue properties varied with the applied load magnitude for both normal and degenerated discs. Overall, our data demonstrate that architectural remodeling stimulated by excessive loading diminishes the disc's ability to resist compression. These results are similar to degeneration-dependent changes reported for human discs.