The distributed permutation flowshop scheduling problem (DPFSP) has attracted a lot of attentions in recent years. Furthermore, sequence-dependent setup time (SDST) often occurs in the job’s production, and total flowtime becomes a more important and meaningful objective for the modern dynamic productive environment. Therefore, the DPFSP with SDST under minimization of total flowtime is investigated in this paper, and the mathematical model is established. To solve the problem, this paper presents three constructive heuristics and an effective discrete artificial bee colony (EDABC) method based on the acceleration. In the EDABC, the constructive heuristics are used to initialize population. Moreover, based on the problem-specific of sequence-dependent, the employed bees stage, onlooker bees stage and scout bees stage are improved by exploring the acceleration methods to evaluate the neighboring solutions. Further, to strengthen the performance of the proposed algorithm, three effective problem-oriented local search methods are developed, including referenced local search (RLS), improved local search 1 (ILS1) and improved local search 2 (ILS2). RLS is used to the best solution after the initialization, and ILS1 and ILS2 are designed in the framework of improved variable neighborhood descent. The extensive computational experiences are carried out, and the results show that the proposed methods, including three heuristics and EDABC, have outstanding performance for the SDST/DPFSP to minimize the total flowtime.