European discovery of the Galápagos Islands occurred when Spanish Whalers killed and captured thousands of the Galápagos tortoises to extract their fat. The tortoises could also be kept on board ship as a means of providing of fresh protein as these animals could survive for several months on board without any food or water. The hunting of the tortoises was responsible for greatly diminishing, and in some cases eliminating, certain species. Along with whalers came the fur-seal hunters who brought the population of this animal close to extinction.

Introduced plants and animals, such as feral goats, cats, and cattle, brought accidentally or willingly to the islands by humans, represent the main threat to Galapagos. Quick to reproduce, these alien species decimate the habitats of native species. The native animals, lacking natural predators on the islands, are defenseless to introduced species and fall prey.

Some of the most harmful introduced plants are the Guayaba or Guava Psidium guajava, avocado Persea americana, cascarilla Cinchona pubescens, balsa Ochroma pyramidale, blackberry Rubus glaucus, various citrus , floripondio Datura arborea, higuerilla Ricinus communis and the elephant grass Pennisetum purpureum. These plants have invaded large areas and eliminated endemic species in the humid zones of San Cristobal, Floreana, Isabela and Santa Cruz. Also, these harmful plants are just a few of introduced species on the Galapagos Islands. There are over 700 introduced plant species today. There are only 500 native and endemic species. This difference is creating a major problem for the islands and the natural species that inhabit them.

Many species were introduced to the Galapagos by pirates. Thor Heyerdahl quotes documents that mention that the Viceroy of Peru, knowing that British pirates ate the goats that they themselves had released in the islands, ordered dogs to be freed there to eliminate the goats. Also, when colonization of Floreana by Jose de Villamil failed, he ordered that the goats, donkeys, cows, and other animals from the farms in Floreana be transferred to other islands for the purpose of later colonization.

Non-native goats, pigs, dogs, rats, cats, mice, sheep, horses, donkeys, cows, poultry, ants, cockroaches, and some parasites inhabit the islands today. Dogs and cats attack the tame birds and destroy nests of birds, land tortoises, and marine turtles. They sometimes kill small Galapagos tortoises and iguanas. Pigs are even more harmful, covering larger areas and destroying the nests of tortoises, turtles and iguanas as well as eating the animals' native food. Pigs also knock down vegetation in their search for roots and insects. This problem abounds in Cerro Azul volcano and Isabela, and in Santiago pigs may be the cause of the disappearance of the land iguanas that were so abundant when Darwin visited. The black rat Rattus rattus attacks small Galapagos tortoises when they leave the nest, so that in Pinzon they stopped the reproduction for a period of more than 50 years; only adults were found on that island. Also, where the black rat is found, the endemic rat has disappeared. Cows and donkeys eat all the available vegetation and compete with native species for the scarce water. In 1959, fishermen introduced one male and two female goats to Pinta island; by 1973 the National Park service estimated the population of goats to be over 30,000 individuals. Goats were also introduced to Marchena in 1967 and to Rabida in 1971. However a recent goat eradication program has cleared most of the goat population from Isabela.

The fast growing poultry industry on the inhabited islands has been cause for concern from local conservationists, who fear that domestic birds could introduce disease into the endemic and wild bird populations.

The Galapagos marine sanctuary is under threat from a host of illegal fishing activities, in addition to other problems of development. The most pressing threat to the Marine Reserve comes from local, mainland and foreign fishing targeting marine life illegally within the Reserve, such as sharks (hammerheads and other species) for their fins, and the harvest of sea cucumbers out of season. Development threatens both land and sea species. The growth of both the tourism industry and local populations fuelled by high birth rates and illegal immigration threaten the wildlife of the Archipelago. The recent grounding of the oil tanker Jessica and the subsequent oil spill brought this threat to world attention.

Currently, the rapidly growing problems, including tourism and a human population explosion, are further destroying habitats.
On January 28, 2008, Galapagos National Park official Victor Carrion announced the killing of 53 sea lions at Pinta, Galapagos Islands nature reserve with their heads caved in. In 2001 poachers killed 35 male sea lions.