Final answer:
The event most often considered to mark the end of the Middle Ages, from the options provided, is the Plague or Black Death that caused significant upheaval and transition in Europe.
Step-by-step explanation:
Many historians consider the fall of Constantinople in 1453, not listed in the options provided, as the definitive end of the Middle Ages. However, if we are to choose from the given events, the Plague, also known as the Black Death, is often seen as a pivotal moment in European history marking the conclusion of the Middle Ages and the transition to the Early Modern period. The devastation caused by the Plague, which killed approximately a third of the European population between 1347 and 1350, led to massive social, economic, and cultural changes that signified a break from the past.
While the Great Schism and The Hundred Years' War were significant, they were more ongoing processes of change rather than a single, defining event like the Plague. The Crusades occurred too early to be considered the end of the Middle Ages. Thus, within the choices provided, the Plague can be seen as the event that most symbolizes the end of this era.