Pasco County was created by the Florida Legislature on May 12, 1887. Previously it had been the southern end of Hernando County, commonly called the "claber end" by early settlers. The new county was named in honor of U.S. Senator Samuel Pasco. A referendum held in 1889 named Dade City as the county seat.

The Pasco County area was inhabited from prehistoric times and contains a large number of archaeological sites showing human occupation as early as 9000 B.C. When Spanish explorers passed through the area in the sixteenth century, it was inhabited by Indian of the Muskegan language group. In the early 1700's, southern Creek Indians (called Seminoles) moved into the area. They were later joined by groups of escaped Negro slaves and remained until the first half of the nineteenth century when they were forcibly removed to Oklahoma or driven south to the Everglades. Among the Seminole Chiefs whose territories included parts of what is now Pasco County were Aripeka, Chipco, and Tiger Tail.

Following the massacre in 1835 of Major Francis Dade and his men by a Seminole war party under the command of Chief Alligator, a fort was built near present-day Lacoochee in Northeastern Pasco County and named in honor of Major Dade. The signing of the Treaty of Fort Dade in 1836 ended the most active phase of the war, and the fort was abandoned in 1839. With the cessation of hostilities and the passage of the Armed Occupation Act of 1842, a number of families settled in the area. In 1845, the Fort Dade post office was established at "White House" plantation in what is now Northeastern Dade City. About the same time the Tucher family planted the first orange grove in the area at their plantation near Richland (then called Tuckertown). In 1849 the U.S. Army rebuilt Fort Dade near the present site of Community General Hospital in Dade City. The fort was used as a refuge for settlers during the Third Seminole Was after an Indian war party attacked the Bradley farm near what is now Darby community in central Pasco County. Two children were killed in the "Bradley Massacre", the last Indian attack on a settler's homestead east of the Mississippi.

Before the coming of the railroads in 1887, the principle communities in Southern Hernando County ( present day Pasco County) were Dade City, Fort Dade, Chipco, Lake Cuddy, San Antonio, Tucker Town and Hudson. The establishment of rail lines through the area made the production and shipment of oranges, tobacco, lumber, and naval stores highly profitable, and a substantial number of small towns developed through out the county. Most of the communities of the 1880's and 1890's disappeared when the virgin pine forests were cut down or after the "great freeze" of 1895, which severely damaged the citrus industry in the area. Tobacco became a principal crop for a period of around twenty years following the "great freeze". The pine lumber and turpentine industries developed more slowly and after 1923, centered around the Cummer Company in Lacoochee, a major employer in the area until the 1960's. Both pine and cypress are still being logged in Pasco County.

The principle communities are Dade City, Zephyrhills, New Port Richey, Port Richey, and San Antonio. Dade City was known as Fort Dade until 1881 when the Fort Dade Postmaster's Commission was transferred to Fort Dade community a few miles west. Zephyrhills was established in 1911 as a retirement center for veterans of the Union Army. New Port Richey was founded in 1915 adjacent to the older town of Port Richey, established by Captain Aaron Richey in the 1880's. San Antonio was developed as the center of the "Catholic Colony" by Judge Edwin Dunne in 1881. Holiday appeared as part of the extension development of the county's west coast in the 1960's.

In the era of the Second World War, the development of Pasco Packing Company (now Lykes-Pasco) and later of Evens Packing Company in Dade City gave the county two of the largest citrus packing plants in the world. The procedure for making orange juice concentrate was, to a large degree, developed at Pasco Packing Company.

The coastal portion of the county was largely undeveloped until the second half of the twentieth century when it became favored as a retirement area. In recent years, huge residential developments have appeared around U.S. Highway 19, causing the county's population center to shift to the west coast.