Alessandro was born at Mulazzo, Tuscany, on November 5th, 1754. He was the son of Carlo Morela Malaspina, marquess of Mulazo, and of Caterina Meli Lupi de Soragna, niece of the viceroy of Sicily Giovanni Fogliani Sforza.

He grew up in Palermo with his great-uncle and eventually went to Rome in 1765 to study at Pio Clementino School. In 1773, once his education completed, he joined the Order of Malta. He stayed on the island for one year, during which he learnt the art of navigation, before following his uncle to the Court of Spain. In 1774, he joined the Spanish Royal Naval Academy in Cadiz as a sailor guard. In 1775-1776, he took part into several operations on the Mediterranean sea (sieges of Melilla and Alger). He was eventually sent on exploration and trade missions which led him three times to the Philippines between 1777 and 1788. He rapidly climbed the ladder of the Spanish Navy,  winning fame on the different seas of the globe and during the siege of Gibraltar against the English in 1780.

Together with his friend Jose de Bustamante y Guerra, he then proposed to King Charles III to lead a political and scientific expedition throughout the whole territory belonging to the Spanish EmpireAccording to the Enlightenment Spirit, the expedition's main goal was to assess the populations and resources of the Spanish Empire in order to have a full knowledge of their extent.  Alessandro worked with numerous European scientists to get ready for his expedition. They eventually embarked upon two frigates, the Atrevida and the Descubierta. After a fifty-two-day-journey, the two ships arrived off the Montevideo coast on September 20th. They sailed along the South-American coasts and eventually passed the Cape Horn and sailed up to the Mexican coasts where they split. Once in Panama harbour, Alessandro studied the possibility of a canal which would be a shortcut between the Atlantic and the Pacific oceans. He eventually resumed his exploration of the American coasts, searching for a route from the north-west which would allow to reach the Atlantic ocean through the islands of Canada Great North. He did not succeed more than James Cook before him, and this route was finally discovered by Roald Amundsen in 1906.

Once in Alaska, he made a stop on Vancouver island, where he signed a friendship treaty with the natives. The two frigates sailed together again through the Pacific Ocean, exploring the Marshall Islands, the Marianas and eventually the Philippines, Macao, New-Zealand and Sydney, before crossing back the ocean. After passing the Cape Horn again, they sailed back to Cadiz on September 21st, 1794. Malaspina was back to Spain with an amount of knowledge never gathered before. Cartographers, botanists, naturalists, astronomers had indeed amassed new information galore, thanks to their meeting native people and local political and scientific leaders. New maps, new sketches and collections of plant and mineral species were exhibited, and the information gathered during each stop of their expedition allowed to know the populations of the Empire better. Thanks to this latest information galore, the king was shown the Empire through different goggles, from the description of the populations to the economical resources and the inventory of all the belongings of the Spanish colonies. Heart and soul of the expedition, Alessandro Malaspina had granted a great freedom of action to the scientists and artists who accompanied him.In December, Alessandro was received at the Escorial by King Charles IV, who appointed him sergeant a few months later. The navigator eventually presented a confidential political report (Viaje político-científico alrededor del Mundo, 1794), in which he developed his views about the management of the Empire and criticised it in order to allow the renovation of an old-fashioned colonial organisation.  Among others, he advised to grant the colonies a larger autonomy and, following the British pattern, he advocated the building of a vast confederation of States enjoying trade agreements. He also put forward a larger religious tolerance and the reorganisation of the administration, which he considered too heavy and corrupt. However, this smart and enlightened reformism brought worries, suspicion and schemes. In November, 1795, Alessandro Malaspina was accused by Manuel Godoy, Charles IV's Prime Minister, of being a revolutionary and of plotting against the crown. Convicted, he got sentenced to ten years' imprisonment at the Castle of San Anton, at la Coruña. This sentence obliged his partners to adjourn their works for several years. While in prison, he wrote several essays of economics and aesthetics, as well as literary reviews.

Released in 1802 under Napoleon's pressure, he went back to his native land, where he dealt with local political matters. In 1805, he became a member of the Council of State of the Kingdom of Italy, founded that same year by Napoleon. He was entrusted the task of organising a cordon sanitaire between the Kingdom of Italy and that of Etrury, where Livorno was going through a yellow fever outbreak. Alessandro Malaspina died at Pontremoli, near Mulazzo where he was born, in April 1810. A glacier in Alaska, as well as a strait and a peninsula in British Columbia were named after the famous navigator.