The end of the Italian Renaissance occurred during the late 15th century through the early 16th century. The period of proliferation of education, science, and the arts came to an end for a number of reasons.

During this time, the Catholic Church controlled much of the wealth that fueled the progressive works created during the Italian Renaissance. As the beliefs of the Catholic Church were questioned by men like Martin Luther, the Protestant Reformation was born. Many, previously staunch, Catholics turned away from the church, which resulted in a reduction in its economic domination. The Counter-Reformation was formed, which stifled the creativity of the great thinkers as they strove to adhere to Catholic teachings out of fear.  

Instead of being one united country, Italy was divided into independent city-states. These independent states were ripe for war with other countries. They were small and less fortified than other countries in Europe. In particular, France waged war against these smaller states, which proved to be costly, and meant there was less money to devote to arts, science, and education. Knowing the implications of the French gaining the wealth of the Italian peninsula, Spain and Germany became involved in the disputes. In 1527, they overtook Rome, which signaled the end of the Papacy and its financial support of the Renaissance.

Successful world exploration also caused the demise of the Italian Renaissance. Christopher Columbus ventured to find a trade route to India, instead finding islands off the coast of South America, which peaked the interest of further exploration. When Vasco da Gama discovered a water route for European trade with India, much of the wealthy trade was diverted from Italy to Portugal and other European countries, leaving the city states of Italy with a sinking economy.

For these reasons, the visionaries and economic means necessary to sustain the Italian Renaissance were stifled, causing it to move away from Italy to other parts of Europe.