On July 5, 1757 he received his doctorate in medicine. From 1757 to 1760 he was interim professor of anatomy in Madrid. During those same years he continued to study botany at the Migas Calientes Botanical Gardens (now the Real Jardín Botánico de Madrid), and also astronomy and mathematics.
After three years he decided to leave for America, as the private physician of the new viceroy of New Granada, Pedro Messía de la Cerda. He sailed on September 7, 1760, arriving at Santa Fe de Bogotá on February 24, 1761. During the long transatlantic passage he began writing his Diario de Observaciones, which he continued until 1791.
From his arrival in the Viceroyalty, Mutis concentrated on his botanical studies, beginning work on an herbal and investigating for cinchona, which was considered a panacea for the treatment of all kinds of diseases. He wrote El Arcano de la Quina.
Mutis led the Royal Botanical Expedition, established in 1783, for 25 years. It explored some 8,000_km² in a range of climates, using the Río Magdalena for access to the interior. He developed a meticulous methodology that included the harvesting of the samples in the field together with detailed descriptions, including data on the surroundings of each species and its utility. Hundreds of plants were discovered and described. More than 8,000 plates, plus maps, correspondence, notes and manuscripts were sent to Spain. His museum consisted of 24,000 dried plants, 5,000 drawings of plants by his pupils, and a collection of woods, shells, resins, minerals, and skins. These treasures arrived safely at Madrid in 105 boxes, and the plants, manuscripts, and drawings were sent to the botanical gardens, where they were relegated to a tool-house.
However much of the work was wasted because the results remained unedited and unanalyzed. Also, the collation between the notes and the plates was lost during the transfer to Spain. His work on the species and varieties of Chinchona had lasting influence.
He determined the longitude of Bogotá by the observation of an eclipse of a satellite of Jupiter and was a major influence on the construction of the national observatory.
In March 1762, at the inauguration of the chair of mathematics at the Colegio del Rosario, he expounded the principles of the Copernican system and of the experimental method of science, leading to a confrontation with the church. In 1774 he had to defend the teaching of the principles of Copernicus, as well as natural philosophy and modern, Newtonian physics and mathematics, before the Inquisition.
Alexander von Humboldt visited Mutis in 1801, during his expedition to America. Humboldt stayed with Mutis for two months, and greatly admired his botanical collection.
Mutis died in Bogotá on September 11, 1808 at 76 years of age, a victim of apoplexy. Because much of his botanical work was lost or unpublished, he is known to history not as a great scientist, but as a great promoter of science and knowledge.
His likeness is well known to Spaniards, because his image was used on the old banknotes of 2,000 pesetas. This was the first in a series of banknotes commemorating Spain in America. On the reverse was a drawing of the Mutisia orchid, named in his honor.
His likeness also appeared on the 200-peso bill in Colombia from 1983 to 1992.
José Celestino Mutis Botanical Gardens, a park and center of scientific investigation, is named in his honor in Bogotá. It includes climate-controlled exhibits of the flora in all climate zones of Colombia. There is also an exhibit of 5,000 Colombian orchids, one of Colombia's greatest and most exquisite showcases.
The town of Bahia Solano on Colombia's Pacific coast in the Department of Choco's official name is Puerto Mutis, in honor of Jose Celestino Mutis. The airport there is Aeropuerto Jose Celestino Mutis, as well. This town is located north of the city of Buenaventura and north of the San Juan River - the largest river in South America to empty into the Pacific Ocean.