A mechanism is provided in a data processing system for pipelined compression of multi-byte frames. The mechanism combines a current cycle of data in an input data stream with at least a portion of a next cycle of data in the input data stream to form a frame of data. The mechanism identifies a plurality of matches in a plurality of dictionary memories. Each match matches a portion of a given substring in the frame of data. The mechanism identifies a subset of matches from the plurality of matches that provides a best coverage of the current cycle of data. The mechanism encodes the frame of data into an encoded output data stream.