A system and method for operating automated guided vehicles (AGVs) and autonomous mobile robots are disclosed. The system for operating AGVs includes: an AGV that loads components in a vehicle manufacturing plant and transfers the components along a set travel path; a programmable logic controller (PLC) located on a production line and at each of a plurality of nodes present on the travel path, and controlling peripheralautomation facilities; and an operation server configured to control the operation of the AGV and each automation facility via the PLC, and to set PLC control conditions for controlling each automation facility in each segment by collecting PLC memory data from the PLC and querying the PLC memory data based on the movement position of the AGV when setting the travel path.