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A continuous 5-sequential completely mixed reactors system was developed to anaerobically digest liquid dairy manure with different organic strength. Within the range of experimental conditions, i.e., influent organic strength (10 to 30 g/L of COD and 0.8% to 2.7% of total solid) and hydraulic retention time (HRT) (0.33 to 15 day), the total amount of biogas and the proportion of methane produced from the first reactor were always at the highest levels, and then decreased with sequential reactors. The liquid pH of all the reactors was maintained at a neutral range (7.2-7.7) with an alkalinity ranging from 3.5 to 4 g CaCO3/L. The profiles of biogas production and liquid pH with the sequential reactors suggested that the two-stage anaerobic digestion process (i.e., acidogenesis reactor produces less biogas with an acidic pH, while the methanogenesis reactor produces more biogas with a neutral pH) could not be implemented by the system developed in this work. The reason was attributed to: (1) the alkalinity of the reactor liquid were at a high level which maintained a neutral liquid pH; and (2) the manure influent contained certain amount of volatile fatty acids (especially acetate), which supplied to the first reactor for the methanogens to produce more biogas than the following reactors. The sequential reactors system was also designed in such a way that the anaerobic digestion performance at different HRT levels could be investigated at a given influent feeding rate and reactor working volume. Between HRT ranging from 0.33 day to 15 day, the specific biogas production rate decreased, while COD and solid removal percentage increased with HRT. It was found that at a specific HRT level, the anaerobic digestion performances (biogas production, COD, TS/VS reduction) of a sequential-reactors combination (approximated as a plug-flow type reactor) were similar to those of a single completely mixed reactor.