Objectives: Safe drinking water, sanitation and hygiene are protective against diarrhoeal disease; a leading cause of child mortality. The main objective was an updated assessment of the impact of unsafe water, sanitation and hygiene (WaSH) on childhood diarrhoeal disease. Methods: We undertook a systematic review of articles published between 1970 and February 2016. Study results were combined and analysed using meta-analysis and meta-regression. Results: A total of 135 studies met the inclusion criteria. Several water, sanitation and hygiene interventions were associated with lower risk of diarrhoeal morbidity. Point-of-use filter interventions with safe storage reduced diarrhoea risk by 61% (RR = 0.39; 95% CI: 0.32, 0.48); piped water to premises of higher quality and continuous availability by 75% and 36% (RR = 0.25 (0.09, 0.67) and 0.64 (0.42, 0.98)), respectively compared to a baseline of unimproved drinking water; sanitation interventions by 25% (RR = 0.75 (0.63, 0.88)) with evidence for greater reductions when high sanitation coverage is reached; and interventions promoting handwashing with soap by 30% (RR = 0.70 (0.64, 0.77)) vs. no intervention. Results of the analysis of sanitation and hygiene interventions are sensitive to certain differences in study methods and conditions. Correcting for non-blinding would reduce the associations with diarrhoea to some extent. Conclusions: Although evidence is limited, results suggest that household connections of water supply and higher levels of community coverage for sanitation appear particularly impactful which is in line with targets of the Sustainable Development Goals.