Techniques for processing unaligned IO requests in data storage systems that provide optimization of inline compression. The disclosed techniques employ an unaligned IO cache, which is used by a data storage system to process unaligned IO requests containing data with sizes that are not multiples of a predetermined block size. By employing the unaligned IO cache while processing such unaligned IO requests, the data storage system can reduce the number of read-modify-write sequences required to process a sequential load of unaligned IO requests, thereby reducing the burden on processing resources of the data storage system.