Background: Chronic back pain (CBP) affects over 80 million people in Europe, contributing to substantial healthcare costs and disability. Understanding modifiable risk factors, such as muscle composition, may aid in prevention and treatment. This study investigates the association between lean muscle mass (LMM) and intermuscular adipose tissue (InterMAT) with CBP using noninvasive whole-body magnetic resonance imaging (MRI). Methods: This cross-sectional analysis used whole-body MRI data from 30,868 participants in the German National Cohort (NAKO), collected between 1 May 2014 and 1 September 2019. CBP was defined as back pain persisting >3 months. LMM and InterMAT were quantified via MRI-based muscle segmentations using a validated deep learning model. Associations were analyzed using mixed logistic regression, adjusting for age, sex, diabetes, dyslipidemia, osteoporosis, osteoarthritis, physical activity, and study site. Findings: Among 27,518 participants (n = 12,193/44.3% female, n = 14,605/55.7% male; median age 49 years IQR 41; 57), 21.8% (n = 6003; n = 2999/50.0% female, n = 3004/50% male; median age 53 years IQR 46; 60) reported CBP, compared to 78.2% (n = 21,515; n = 9194/42.7% female, n = 12,321/57.3% male; median age 48 years IQR 39; 56) who did not. CBP prevalence was highest in those with low (<500 MET min/week) or high (>5000 MET min/week) self-reported physical activity levels (24.6% (n = 10,892) and 22.0% (n = 3800), respectively) compared to moderate (500–5000 MET min/week) levels (19.4% (n = 12,826); p < 0.0001). Adjusted analyses revealed that a higher InterMAT (OR 1.22 per 2-unit Z-score; 95% CI 1.13–1.30; p < 0.0001) was associated with an increased likelihood of chronic back pain (CBP), whereas higher lean muscle mass (LMM) (OR 0.87 per 2-unit Z-score; 95% CI 0.79–0.95; p = 0.003) was associated with a reduced likelihood of CBP. Stratified analyses confirmed these associations persisted in individuals with osteoarthritis (OA-CBP LMM: 22.9 cm³/kg/m; InterMAT: 7.53% vs OA-No CBP LMM: 24.3 cm³/kg/m; InterMAT: 6.96% both p < 0.0001) and osteoporosis (OP-CBP LMM: 20.9 cm³/kg/m; InterMAT: 8.43% vs OP-No CBP LMM: 21.3 cm³/kg/m; InterMAT: 7.9% p = 0.16 and p = 0.0019). Higher pain intensity (Pain Intensity Numerical Rating Scale ≥4) correlated with lower LMM (2-unit Z-score deviation = OR, 0.63; 95% CI, 0.57–0.70; p < 0.0001) and higher InterMAT (2-unit Z-score deviation = OR, 1.22; 95% CI, 1.13–1.30; p < 0.0001), independent of physical activity, osteoporosis and osteoarthritis. Interpretation: This large, population-based study highlights the associations of InterMAT and LMM with CBP. Given the limitations of the cross-sectional design, our findings can be seen as an impetus for further causal investigations within a broader, multidisciplinary framework to guide future research toward improved prevention and treatment. Funding: The NAKO is funded by the Federal Ministry of Education and Research(BMBF) [project funding reference numbers: 01ER1301A/B/C, 01ER1511D, 01ER1801A/B/C/D and 01ER2301A/B/C], federal states of Germany and the Helmholtz Association, the participating universities and the institutes of the Leibniz Association.