The city now known as DeLand was originally called Persimmon Hollow. Henry DeLand, a successful businessman from New York, moved to Persimmon Hollow in 1876. Mr. DeLand donated land and money for many community and cultural projects, including initiating the first school.

In 1880, a strong hurricane hit DeLand, littering the streets with debris and damaging numerous citrus groves in the area. DeLand was incorporated as a city in 1882, and at the same time, Stetson University began as DeLand Academy.

In 1886, the railroad was extended to the town. That same year, a major fire started in the Wilcox Saloon, which was a "typical" wooden frame building that had sawdust on the floor. The fire destroyed an entire block of Woodland Boulevard downtown. As a result, the city commission passed two ordinances: 1) only masonry buildings were to be built in the downtown area, and 2) saloons were no longer allowed within the city limits of DeLand.

In 1888, DeLand replaced Enterprise as the Volusia County seat. The freeze of 1894-95 devastated the citrus industry, which had been the livelihood of many DeLand residents. Henry DeLand felt responsible for having encouraged many people to settle in town, so he used up his own fortune helping them recover from the freeze. He moved back to New York to earn money, but he died there in 1908.

Orange City was founded in 1866, and in 1867 its residents wanted to call the new community "Blue Spring." Orange City prospered in the late 1800s. In 1909, a large fire destroyed many of the city's buildings, but the city recovered and continued to grow.

During the Seminole Wars, Sanford was the site of a U.S. Army post called Fort Mellon. As settlers moved into the area, the town of Mellonville was established. When Orange County was created in 1845, Mellonville became the county seat.

In 1870, Henry Shelton Sanford, planning a new city that he hoped would become a gateway city to South Florida, purchased land west of Mellonville. In 1877, the city of Sanford was incorporated and Mellonville was annexed into the city six years later. A short time later, Mr. Sanford formed a land company in London to encourage investments in the new city. That same year, construction began on the South Florida Railroad, with the northern ending point at Sanford, and by 1884 Sanford was a prosperous town with wharves, a railroad and a large hotel.

In 1887, a bakery on First Street caught fire. The blaze spread quickly through the wooden buildings on the east side of town until stopped by the volunteer fire department. When the town was rebuilt, the new structures were made of brick.

During the winter of 1894-95, freezing temperatures destroyed the year's entire citrus crop. Many residents who lost their livelihood left the area, but those who stayed developed a sub-irrigation center that allowed for commercial agriculture. By the first decade of the 20th century, Sanford was one of the largest vegetable shipping centers in the United States and was called "The Celery City" after its most successful crop. In 1913, Seminole County was officially established with Sanford as its county seat.

The first permanent settlement in the area was established by Dr. Andrew Turnbull in 1768. Turnbull recruited settlers from Smyrna, Turkey (a Greek, or Hellenistic, settlement), Italy and Minorca. Turnbull had the settlers dig several canals, the remains of which can be still seen today. These settlers were mistreated, however, and by the mid-1770s, many escaped to St. Augustine.

Ambrose Hull from Connecticut obtained a large piece of land from the Spanish in 1802. Hull's stone plantation was destroyed in the "Patriot's War" of 1812, and he left the area. Hull was followed by settlers from the Bahamas.

A few families continued to live in the New Smyrna area, establishing sugar plantations. After the Civil War, New Smyrna began to grow and prosper and was incorporated into a city in 1887. The railroad came to New Smyrna in the 1890s. The downtown district was spared from major fires that spread through other towns, but a large boardinghouse on Canal Street downtown did go up in flames.