The principal parameters influencing anaerobic digestion (AD) of sewage sludge have been extensively studied in controlled laboratory experiments, but the effects of sludge composition on full-scale systems have received relatively little attention. Sludge samples from eight major wastewater treatment plants (WWTPs) in the UK were examined to determine the effects of sludge composition on digestion performance. The biogas yield (BY) was estimated by two different methods: (1) a standard approach based on the reduction in volatile solids (VS), and (2) a more detailed mass balance of major constituent fractions of organic matter in sludge. The results showed that BY increased significantly with the overall amount of VS contained in digester feed sludge. In terms of the effects of individual fractions, BY was significantly related to and increased with the fat and cellulose contents in raw sludge, consistent with the high calorific value of fat and the digestibilities of both substrates, relative to the other major organic components. The results demonstrated the importance of sludge composition on digester performance and strategies to maximise BY were identified, for instance, by increasing codigestion of high fat containing substrates, and by utilising fat, oil and grease collected in-sewer and at WWTP.