Spaniards first arrived in the Aburrá Valley in the 1540s, but Medellín was not founded until 1616. Historians believe that many early settlers were Spanish Jews fleeing the Inquisition. They divided the land into small haciendas (country estates), which they farmed themselves – something that was very different from the slave-based plantation culture that dominated much of Colombia. With their focus on self-reliance, these early paisas came to be known as hard workers with a fierce independent streak – traits they've exported throughout the Zona Cafetera.

Medellín became the capital of Antioquia in 1826 but long remained a provincial backwater, which explains why its colonial buildings are neither sumptuous nor numerous. The city's rapid growth began only at the start of the 20th century, when the arrival of the railroad, together with a highly profitable boom in coffee production, quickly transformed the city. Mine owners and coffee barons invested their profits in a nascent textile industry, and their gamble paid off. Within a few decades, Medellín had become a large metropolitan city.

By the 1980s the city's entrepreneurial spirit was showing its dark side. Under the violent leadership of Pablo Escobar, Medellín became the capital of the world's cocaine business. Gun battles were common, and the city's homicide rate was among the highest on the planet. The beginning of the end of the violence came with Escobar's death in 1993, and today Medellín is one of the most accessible destinations in the country.