Background: High levels of sedentary behaviour are an emerging global public health concern, but its impact on cancer risk remains unclear. Methods: Within the Global Cancer Update Programme (CUP Global), we systematically searched the literature in PubMed and Embase until September 2024 for observational cohort studies on sedentary behaviour and adult cancer risk. Using dose-response meta-analyses, we investigated sedentary behaviour domains (total, occupational, recreational, transportation, and/or other) and dimensions (duration, frequency), and additionally pooled across domains. The quality of evidence was graded by the CUP Global Expert Panel (protocol registration: https://osf.io/7utbm/). Findings: We identified 62 publications from 27 cohorts comprising 162,902 incident cancer cases across 19 anatomical sites. There was evidence for a probable causal positive association between sedentary time (mixed definitions) and breast (RRper 2 hours/day=1.03; 95%CI=1.02-1.05; I2=10%; n=11 studies) and colon (RR=1.05; 95%CI=1.03-1.07; I2=0%; n=9) cancer risk, and between television watching time and colon cancer risk (RRper 2 hours/day=1.08; 95%CI=1.05-1.11; I2=0%; n=6). Limited suggestive evidence supported positive associations between sedentary time (mixed definitions) and lung (RR=1.04; 95%CI=1.00-1.09; I2=69%; n=7), ovarian (RR=1.06; 95%CI=1.01-1.10; I2=0%; n=7), premenopausal (RR=1.03; 95%CI=0.99-1.08; I2=20%; n=7) and postmenopausal breast (RR=1.02; 95%CI=1.00-1.04; I2=7%; n=11), and colorectal (RR=1.02; 95%CI=1.00-1.04; I2=47%; n=11) cancers, and between occupational sitting time and breast (RRper 2 hours/day=1.05; 95%CI=1.01-1.09; I2=0%; n=4) and colon (RR=1.08; 95%CI=1.02-1.15; I2=28%; n=2) cancers. An interactive evidence platform is available at: https://teacup.cc.ic.ac.uk/sedentary-behaviour-cancer.html. Interpretation: Evidence supports that prolonged sedentary behaviour is probably a cause of breast and colon cancers, while limited suggestive evidence supports positive associations for several other exposure-cancer pairs, including lung and ovarian cancers. This evidence should lead to revised cancer prevention recommendations. Future research should focus on device-based exposure assessments, repeated measurements, exposure substitution models, inclusion of diverse populations and investigation of biological mechanisms.