[6] Along with neighboring Rehoboth Beach, Lewes is one of the principal cities of Delaware's rapidly growing Cape Region.

Lewes was the site of the first European settlement in Delaware, a whaling and trading post that Dutch settlers founded on June 3, 1631, and named Zwaanendael (Swan Valley).

[7] The colony had a short existence, as a local tribe of Lenape Indians killed all 32 settlers in 1632.

The area remained rather neglected by the Dutch until, under the threat of annexation from the colony of Maryland, the city of Amsterdam made a grant of land at the Hoernkills (the area around Cape Henlopen, near the current town of Lewes) to a group of Mennonites for settlement in 1662.

A total of 35 men were to be included in the settlement, led by a Pieter Cornelisz Plockhoy of Zierikzee and funded by a sizable loan from the city to get them established.

[8] The Dutch colonists proved slow to regroup, but a new settlement gradually regrew around the Hoernkills.

In late December 1673, when the area was briefly held again by the Dutch, the settlement was attacked and burned down again by a group of Maryland colonists.

In 1682, the Delaware colonies were given to William Penn by King Charles II as payment for a family debt.

[10][11][12][13] On April 6 and 7, 1813, during the War of 1812, Royal Navy vessels led by HMS Poictiers under the command of Captain Sir John Beresford briefly and ineffectually bombarded the town.

"[14][15] In 1941, the United States built Fort Miles on Cape Henlopen, immediately east of Lewes, to defend Delaware Bay and the Delaware River and the oil refineries and factories on its shores, as well as the city of Philadelphia.

Fort Miles never saw any major action; except for range practice, it fired its guns only once between its establishment and the end of World War II.

In addition to Fort Miles, the Cape Henlopen Archeological District, Coleman House, Cool Spring Presbyterian Church, De Vries Palisade, Delaware Breakwater and Lewes Harbor, Fisher Homestead, Fisher's Paradise, Col. David Hall House, Hopkins Covered Bridge Farm, Lewes Historic District, Lewes Presbyterian Church, Lightship WAL 539, Maull House, National Harbor of Refuge and Delaware Breakwater Harbor Historic District, Pagan Creek Dike, Roosevelt Inlet Shipwreck, William Russell House, St. George's Chapel, Lewes, Townsend Site, and Wolfe's Neck Site are listed on the National Register of Historic Places.

Ebe Walters Tunnell moved to Lewes in 1873 to enter the drug and hardware business in part of the old Caleb Rodney House on Second Street.

[31] Lewes serves as a vacation and resort spot popular with residents of Washington, D.C., and the surrounding suburbs.

It features multiple restaurants and bait shops, and in season the dock hosts hundreds of boats from all over.

The town also see the occasional Delaware Natural Resource Police officer patrolling the waterways, and the state park.

[36][38] Cape Water Tours & Taxi operates a round-trip water taxi service between Lewes and Dewey Beach via the Lewes and Rehoboth Canal on Friday evenings in the summer months, offering access to dining and nightlife in Dewey Beach.

The Route 305 "Beach Connection" bus provides service on weekends and holidays in the summer to the Lewes Transit Center Park and Ride from Wilmington, the Christiana Mall, Middletown, and Dover.

[42][43] The Delaware River and Bay Authority operates a shuttle bus route in the summer months that connects the Cape May–Lewes Ferry to the Tanger Outlets and Rehoboth Beach.

[45][46] Lewes was served by a branch of the Delaware Coast Line Railroad that originated in Georgetown, whereupon transfers could be made to trains north to Dover and Wilmington.

[36] Passenger trains operated on this branch by its predecessor company, the Pennsylvania Railroad, but ended between 1936 and 1938.

It followed a path through Milton, Ellendale, Greenwood, crossing the state border into Maryland, then continuing further west to Love Point, whereupon travelers would connect with a ferry to Baltimore.

[53][54] The Lewes Board of Public Works (BPW) provides electricity, water, and sewer service to the city.

[60] Beebe Healthcare Medical Center is located in Lewes, founded in 1916 by the brothers, Drs.

[62] On August 21, 2013, a helicopter reportedly dumped $10,000 in multiple dollar bill denominations over Lewes Harbor in the fulfillment of a deceased local resident's last wish.