One difference between the two series is their target age. The Story of the World is primarily for elementary students, with Volume I recommended for 1st through 4th grade and Volume IV for 4th through 8th grade. The Mystery of History's reading level begins at about 4th or 5th grade in Volume I and progresses to 10th or 11th grade in Volume IV, although it is easily adaptable for multiple ages.
Another key difference is the religious perspective. The Story of the World aims to narrate from a neutral perspective. It covers major religious characters and historical events but does not endorse a particular religious view. The Mystery of History is written from a clearly Christian perspective and integrates biblical and church history into the text.
A minor difference between the two series is the student work involved. The Story of the World revolves around the narrative, so all activities, while engaging, are optional. The Mystery of History is also narrative-based but expects more student work. Nonetheless, it is highly adaptable to each student's age and family preferences.