Sanlúcar lost much of its strategic value after 1645 because of the disgrace of the House of Medina Sidonia, the general decline of Spain under Charles II, the relocation of the Casa de Contratación to the town of Cadiz in 1717, and the Lisbon earthquake of 1755.

Since the restoration of democracy (1975–1982) its town council has borrowed heavily, making Sanlúcar the city with the lowest per capita income in Spain.

The city is part of the tourist area known as the Costa de la Luz (Coast of the Light), about 44 km from the provincial capital of Cádiz.

After the discovery of the New World, Sanlúcar developed as a port for refitting ships, and was the point of departure for various Spanish conquistadors.

Another historical departure was that of Ferdinand Magellan on 10 August 1519, who with a fleet of five ships under his command left Seville and traveled down the Guadalquivir to Sanlúcar de Barrameda at its mouth, where they remained more than five weeks.

These two occupations were naturally concentrated in different parts of the town, and until the modernizing trends of the last few decades, there were marked distinctions between the people living in each area.

People living in the higher elevations away from the sea, in a part of the town known as the Barrio Alto, formerly dedicated themselves exclusively to agriculture.

However, with the advent of mechanisation this sector requires less manpower throughout the year, and most farm workers now work only seasonally during the grape harvest, in the so-called "sherry triangle".

Sanlúcar was then a popular beach resort; presently the people living in this area are generally linked to local wine-making interests and the tourist industry.

Within the park lies the Marisma de Hinojos (Salt Marsh of Fennel Plants); also within its precincts is the possible site of the legendary lost city of Tartessos, the capital of an ancient civilization that predated the Phoenicians in Iberia.