The island has a karst landscape supporting sclerophyllous shrubland. Some limited afforestation with pine trees has been carried out. The sand-dunes at Santa Maria bay retain some native vegetation, including Vitex and Tamarix trees. The island has been identified as an Important Bird Area (IBA) by BirdLife International because it supports 50–80 breeding pairs of yelkouan shearwaters.
Human population on the island is of only 3 permanent residents, since May 2017, after the death of Maria Said at age 90 in the same month.
Comino is known to have been inhabited by farmers during Roman times, but for long periods in its history it has been sparsely populated, privately owned, or abandoned entirely.
Its rugged coastline is delineated by sheer limestone cliffs, and dotted with deep caves which were popular with pirates and marauders in the Middle Ages. The caves and coves of Comino were frequently used as staging posts for raids on hapless boats crossing between Malta and Gozo. In later years, the Knights of Malta used this island as hunting and recreational grounds. The Knights were fiercely protective of the local game, which consisted of wild boar and hares (Maltese: fenek tal-grixti): upon conviction, poachers were liable to a penalty of three years as a galley slave.
From 1285 until some time after 1290, Comino was the home of exiled prophetic cabbalist Abraham Abulafia. It was on Comino that Abulafia composed his "Sefer ha-Ot" (The Book of the Sign), and his last work, "Imre Shefer" (Words of Beauty). In the 16th and 17th centuries, Comino served as a place of imprisonment or exile for errant knights. Knights who were convicted of minor crimes were occasionally sentenced to the lonely and dangerous task of manning St. Mary's Tower.
During the French occupation of Malta, Comino served as a quarantine and existing buildings served as an isolation hospital.
In the past, and well into the 20th century, whenever the seas were too rough for the Gozitan priest to make the crossing to Comino for the celebration of Holy Mass, the local community would gather on the rocks at a part of the Island known as Tal-Ħmara, and gaze across the channel towards the Chapel of Our Lady of the Rocks (Maltese: il-Madonna tal-Blat), in Ħondoq ir-Rummien, Gozo, where Mass was being celebrated. They followed along with the progression of the Mass by means of a complex flag code.
On 6 March 1889 the British battleship HMS Sultan grounded on an uncharted rock in the Comino Channel, ripping her bottom open. She slowly flooded and, in a gale on 14 March 1889 she slipped off the rock and sank. The Italian firm of Baghino & Co raised her in August 1889 for a fee of £50,000. On 27 August Sultan was brought into Malta.
Saint Mary's Tower is the most visible structure on the island. Its background dates back to 1416, when the Maltese petitioned their king, Alfonso V of Aragon, to build a tower on Comino to serve as an early warning system in case of invasion, and to deter marauding Turks, pirates, smugglers and corsairs from using Comino as a hiding place and staging ground for devastating sorties onto the sister islands of Malta and Gozo. Two years later the king levied a special tax on imported wine to raise funds for this project, but diverted the monies into his coffers; the island remained undefended for another two hundred years.
Finally, in 1618 the Knights of Malta under Grandmaster Wignacourt erected St Mary's Tower (Maltese: it-Torri ta' Santa Marija), located roughly in the center of the southern coast of the island. The tower formed part of a chain of defensive towers — the Wignacourt, Lascaris, and De Redin towers — located at vantage points along the coastline of the Maltese Islands, and greatly improved communications between Malta and Gozo. The tower is a large, square building with four corner turrets, located about 80 m (262 ft) above sea level. The Tower itself is about 12 m (39 ft) tall, with walls that are approximately 6 m (20 ft) thick, and is raised on a platform and plinth that are approximately 8 m (26 ft) high.
During the French Blockade (1798–1800), St Mary's Tower served as a prison for suspected spies. In 1829 the British Military abandoned the site. For several decades it was deemed to be property of the local civil authorities, and may have been used as an isolation hospital, or even as a wintering pen for farm animals. The tower again saw active service during both World War I and World War II. Since 1982 the tower has been the property of the Armed Forces of Malta. It now serves as a lookout and staging post to guard against contraband and the illegal hunting of migratory birds at sea.
St Mary's Tower underwent extensive restoration between 2002 and 2004. Today, it remains the most notable structure on Comino, and provides a destination for tourists taking walks around the Island.
A tiny Roman Catholic chapel dedicated to the Holy Family Upon its Return from Egypt is located above Santa Marija Bay. Built in 1618, and enlarged in 1667 and again in 1716, the chapel was originally dedicated to the Annunciation. It has been deconsecrated and reconsecrated at least once in its history, when Comino was devoid of residents. The earliest record of a chapel on this site dates back to the 12th century, and can be seen in a navigational map of the period, located in the National Maritime Museum and Royal Observatory in Greenwich, London. Mass is celebrated in the chapel on Saturday nights and Sunday mornings for the residents, hotel staff and tourists.
Saint Mary's Battery, built in 1716, at the same time as various other batteries around the coastline of mainland Malta and Gozo, is situated facing the South Comino Channel. It is a semi-circular structure with a number of embrasures facing the sea. The Battery still houses two 24-pound iron cannon, and remains in a fair state of preservation mainly due to its remote location. Its armament originally included four 6-pound iron cannon. The Battery underwent restoration in 1996 by the Maltese heritage preservation society, Din l-Art Ħelwa. Saint Mary's Redoubt, an additional defensive structure, was also constructed in 1716 on the northern coast of Comino, however it was subsequently demolished. The Knights also constructed army barracks on Comino. In the early 20th century the barracks were periodically used as an isolation hospital.
Comino Hotel, with its two private beaches, a 1960s development, is located above San Niklaw Bay. There are also holiday bungalows by Santa Marija Bay. There is a police station located between the holiday bungalows and the chapel.
Between Comino and adjacent islet of Cominotto (Maltese: Kemmunett) lie the transparent, cyan waters of the Blue Lagoon (Maltese: Bejn il-Kmiemen, literally "Between the Cominos"). Frequented by large numbers of tourists and tour boats daily, the Blue Lagoon is a picturesque bay with a white sandy base and rich marine life. It is popular with divers, snorkelers and swimmers. Other beaches on Comino include Santa Maria Bay (Maltese: Ramla ta' Santa Marija) and St. Nicholas Bay (Maltese: Bajja San Niklaw).
Comino is a popular location for filmmakers. It appears in the films Troy, The Count Of Monte Cristo and Swept Away. Most notably, St. Mary's Tower on Comino was featured in the film The Count of Monte Cristo, where it doubled as the Château d'If.