Flexible head-end chassis supporting automatic identification and interconnection of radio interface modules (RIMs) and optical interface modules (OIMs) in an optical fiber-based distributed antenna system (DAS) are disclosed. In one embodiment, the flexible head-end chassis includes a plurality of module slots each configured to receive either a RIM or an OIM. A chassis control system identifies an inserted RIM or OIM to determine the type of module inserted. Based on the identification of the inserted RIM or OIM, the chassis control system interconnects the inserted RIM or OIM to related combiners and splitters in head-end equipment for the RIM or OIM to receive downlink communication signals and uplink communications signals for processing and distribution in the optical fiber-based DAS. In this manner, the optical fiber-based DAS can easily be configured or reconfigured with different combinations of RIMs and OIMs to support the desired communications services and/or number of remote units.