In the 8th century a brick and mortar lighthouse at Kodiakkarai (கோடியக்கரை) was said to have been built during the regime of Raja Raja Chola I. In 1890 the British erected a 13-metre (43 ft) lighthouse at Kodiakkarai (கோடியக்கரை) which is still in use near the remains of the old Chola lighthouse.

Before 1968 AD Ptolemy referred to Point Calimere as Calligicum prom.. Use of the term Point Calimere appears to date back at least to between the early 16th century, when Portuguese traders started commercial contacts with nearby Nagapattinam town, and 1554 when they established a commercial center there. In the Portuguese language calido means warm and mar means sea.

Before 1892 the forests around Point Calimere were administered by the Revenue Department and Temple trustees who allowed local people to collect firewood, fish and minor forest products. Forest management practices in the area began in 1892 with creation of the 14.75-square-kilometre (5.70 sq mi) Kodaikadu Reserved Forest. A small area near the Sanyasin Muniaswar Temple was used by the British as a hunting ground and later cleared and replanted with casuarina and eucalyptus for firewood production. Some of these old trees remain. Palmyrah trees were planted to mark the village forests from the Reserved Forest near Munniappan Lake. There is a shrine to the deities Shevrayan and Soni located deep in the forests of the northern part of the sanctuary. A small village near the Shevrayan Kovil shrine was relocated outside the sanctuary after the creation of the Kodaikarai Reserve Forest. A few uncommon Indian tulip and neem trees from this old settlement still remain.

In the early 1900s small numbers of ponies were bred and large amounts of tobacco were grown in the neighborhood. The promontory was once used as a sanitarium, but by 1909 was said to be malarious from April to June. Bathing in the sea at Point Calimere was considered sacred by Hindus and a temple there was an object of pilgrimage.

In 1911 The reserve forest was under the control of the Trichy-cum-Thanjavor Forest Division. In 1922 the reserved forest was put under the control of the Revenue Divisional Officer, Mannargudi by the Governor of Madras. In 1938, Kodaikarai Extension No. 1 23.66 square kilometers (9.14 sq mi), Kodaikarai Extension No. 214.75 0.1 square kilometers (0.039 sq mi), and Kodaikarai Extension No. 3 0.07 square kilometers (0.027 sq mi) were added to form the present area of the sanctuary. In 1950 control of the forest was shifted to the Tiruchirapalli Forest Division, in 1957 to the Thanjavur Division and in 1965 to the State Wildlife officer in Chennai. In 1962 Dr. Salim Ali first identified The Point Calimere region as an area of high significance for the conservation of birds. In 1967 the sanctuary was created and put under control of the Thanjavur Forest Division and then to the Wildlife Division in Nagapattinam when that was created in 1986.

In 1936 a rail line was extended to Kodaikorai for transport of salt from Vedaranyam. Train service was halted in 1988 and the tracks were dismantled in 1995. During World War II a radar station was constructed and operated by Army personnel who had unquestioned access to the forests. In 1943 an experimental Casurina plantation was begun and soon extended by destruction of most of the natural forest. This resulted in a major decrease in numbers and variety of wild animals in the area.

In the early years of the Sanctuary management was concentrated on prevention of poaching and provision of water to the wildlife. Poaching has been controlled but water supply is a continuing effort. In 1979 the first of several water troughs supplied from water barrels transported by bullock cart and open wells were built. Beginning in 2001–02 several perennial water holes supplied by pipe from bore wells and a large elevated water tank on the western edge of the sanctuary were built.

Several tree planting schemes to increase biodiversity have yielded poor results, with the exception of Casuarina equisetifolia. Current practice is to avoid new tree planting and concentrate on removal of the invasive Prosopis juliflora. An annual wildlife census has been conducted since 1991.

The Bombay Natural History Society has been conducting regular bird migration studies in the sanctuary since 1959. In 2007 it is building a new field station in Kodaikadu.

On 9 March 1998 a 45-metre (148 ft) modern lighthouse near Kodaikorai Beach was commissioned.

In 1999 many speed breakers were installed on the Vedaranyam – Kodaikorai road which have effectively prevented the killing of wildlife by speeding vehicles. In 2004/05 nearly 100 boundary pillars were erected for boundary demarcation.

On 26 December 2004 a tsunami as high as 3 metres (10 ft) hit the Kodiyakarai coast of the sanctuary. Seawater flooded the entire sanctuary with four feet of water. The sanctuary escaped serious damage and the sanctuary, animals and birds largely survived the giant wave, but 5,525 people were killed in neighbouring parts of Nagapattinam District.

The documentary film Point Calimere – Little Kingdom by the Coast by Shekar Dattatri won the Centre for Media Studies (CMS) Vatavaran 2007 award in the Nature category.