Intervertebral disc degeneration, local lumbar segmental morphology changes, and atrophy of multifidus muscle have been considered to be associated with degenerative lumbar spondylolisthesis. However, there remains a great deal of controversy. To further investigate their relationship with degenerative lumbar spondylolisthesis, we conducted a retrospective study that included 67 patients with degenerative spondylolisthesis and 182 control subjects. Propensity score matching was employed to match the case group and the control group. Disc height was evaluated by the anterior disc height index (DHIA) and posterior disc height index (DHIP). Local lumbar segmental morphology was assessed by segmental lordosis (SL). The fatty infiltration and atrophy of multifidus muscle was evaluated by multifidus muscle net content (MFNC). Our results indicate that DHIA, DHIP, SL, and MFNC in the case group were significantly lower than in the control group. Furthermore, the DHIA, DHIP, and MFNC of the slipped segment (L4/5) were lower than those of the non-slipped segment (L3/4). Correlation analysis showed a high relationship between DHIA and MFNC and the degree of degenerative lumbar spondylolisthesis. Logistic regression analysis revealed that DHIA and MFNC might act as protective factors against the development of degenerative lumbar spondylolisthesis. Additionally, a prognostic nomogram was developed and validated to assess the likelihood of patients with severe symptoms requiring surgical intervention.© 2023. The Author(s).