Methods for performing packet classification via prefix pair bit vectors. Unique prefix pairs in an access control list (ACL) are identified, with each prefix pair comprising a unique combination of a source prefix and a destination prefix. Corresponding prefix pair bit vectors (PPBVs) are defined for each unique source prefix and unique destination prefix in the ACL, with each PPBV including a string of bits and each bit position in the string associated with a corresponding prefix pair. A list of transport field value combinations are associated with each prefix pair based on corresponding entries in the ACL. During packet-processing operations, PPBV lookups are made using the source and destination prefix header values, and the PPBVs are logically ANDed to identify applicable prefix pairs. A search is then performed on transport field value combinations corresponding to the prefix pairs and the packet header to identify a highest priority rule.