Known as the "Historic Waterfront Gateway City", Sanford sits on the southern shore of Lake Monroe at the head of navigation on the St. Johns River.

During the Second Seminole War in 1836, the United States Army established Camp Monroe and built a road now known as Mellonville Avenue.

In 1835, the Seminoles burned the port of Palatka on the St. Johns River, then the major artery into Central Florida from the East Coast.

General Zachary Taylor had a road built connecting a string of defenses from Lake Monroe to Fort Brooke (now Tampa).

Sanford imported two colonies of Swedes (totaling about 150 adults) as indentured servants to labor a year for their travel expenses.

[4] The Swedes would do the back-breaking work of establishing a new town and clearing the sub-tropical wilderness in advance of creating a citrus empire, arriving by steamboat in 1871.

In April of that year, President Chester A. Arthur arrived by steamer to vacation for a week at the Sanford House, a lakeside hotel built in 1875 and expanded in 1882.

The South Florida Railroad opened a narrow-gauge route from Sanford to Orlando in 1880, and eventually built a connection to the Port of Tampa by the end of 1883.

On December 1, 1891, merchant William Clark and registered African American voters of Goldsboro incorporated as a town just to the southwest of Sanford.

A.M. Deforest attempted to revive the library project with the aid of the Wednesday Club, the president, Mrs. Brown encouraged the women to begin fundraising efforts.

At its peak in 1943–45, NAS Sanford was home to approximately 360 officers, 1500 enlisted men and 150 WAVES and included an auxiliary airfield to the east near Lake Harney known as Outlying Field Osceola.

A major construction program ensued, with NAS Sanford redeveloped as a Master Jet Base for carrier-based Douglas A-3 Skywarrior and later North American A-5A and RA-5C Vigilante aircraft.

At its peak in the mid-1960s, the base was home to nearly 4000 military personnel, comprising the air station personnel complement, an Aircraft Intermediate Maintenance Department, the Navy Dispensary, the Marine Barracks, a Replacement Air Group/Fleet Replacement Squadron for the RA-5C, and nine deployable Fleet RA-5C squadrons that routinely deployed aboard large aircraft carriers to the Mediterranean and the Pacific.

As a result of the increasing costs of the Vietnam War and concurrent federal domestic spending related to President Lyndon Johnson's Great Society social programs, NAS Sanford was one of several stateside military installations identified for closure by the Department of Defense in 1967.

Flight operations were rapidly scaled down during 1968 as the squadrons of Reconnaissance Attack Wing ONE transferred to the former Turner AFB, renamed Naval Air Station Albany, Georgia.

This resulted in a significant economic downturn for the City of Sanford and Seminole County with the departure of all military personnel and their families.

The Navy's presence is commemorated at the airport by two historical markers and the NAS Sanford Memorial Park, which was dedicated on Memorial Day in May 2003 and includes a restored RA-5C Vigilante on loan from the National Naval Aviation Museum that was placed on permanent static display at the entrance to the commercial airline terminal.

But because of Sanford's former preeminence as a trade center, the city retains a significant collection of older commercial and residential architecture, on streets shaded by live oaks hung with Spanish moss.

Robinson joined his team despite the threat, but the uproar from the mainly white audience in the stands caused him to be escorted off the field and he was not able to play.

Other Major League stars have played in the Sanford stadiums, including Babe Ruth, Willie Mays, Tim Raines, and David Eckstein.

[28] Sanford is the southern terminus of Amtrak's Auto Train which conveys Eastern Seaboard travelers and their vehicles to Lorton, Virginia, about 25 miles (40 km) south of Washington, D.C.

[29] SunRail, the Central Florida commuter rail system, serves the city out of a new station off State Road 46.

The State Road 417 or Seminole Expressway begins in Sanford at Interstate 4 and forms the Eastern Beltway around Orlando ending at Walt Disney World Resort.

The ten-foot wide paved walkway spans a distance of several miles in Sanford's downtown area along the waterfront of Lake Monroe.

The city completed multimillion-dollar streetscapes of 1st Street and Sanford Avenue in its historic downtown, using brick pavers, creating wider sidewalks, and adding trees, flowers, and benches.