As all other naval officers' wives, Maria spent several years ashore, seldom seeing her husband. Most of these years she lived in London. But while other officers’ wives spent their time with domestic chores, she worked as a translator and book editor. In 1819 she lived in Italy for a time, which resulted in the book Three Months Passed in the Mountains East of Rome, during the Year 1819. Being very interested in the arts, she also wrote a book about the French baroque painter Nicolas Poussin, Memoirs of the Life of Nicholas Poussin (French first names were usually Anglicised in those days), in 1820.

In 1821 Maria was invited to accompany her husband aboard HMS Doris, a 36 gun frigate under his command. The destination was Chile, and the purpose was to protect British mercantile interests in the area. In April 1822, shortly after the ship had rounded Cape Horn, her husband died of a fever, so HMS Doris arrived in Valparaiso without a captain, but with a distraught captain’s widow. All the naval officers stationed in Valparaiso — British, Chilean and American — tried to help Maria (one American captain even offered to sail her back to Britain), but she was determined to manage on her own. She rented a small cottage, turned her back on the English colony ("I say nothing of the English here, because I do not know them except as very civil vulgar people, with one or two exceptions", she later wrote), and lived among the Chileans for a whole year. Later in 1822, she experienced one of Chile’s worst earthquakes in history, and recorded its effects in detail — something nobody had done before.

In 1823 she began her journey back to Britain. She made a stop in Brazil and was introduced to the newly appointed Brazilian emperor and his family. The year before, the Brazilians had declared independence from Portugal and had asked the resident Portuguese crown prince, Dom Pedro to become their emperor. It was agreed that Maria should become the tutor of the young princess Donna Maria, so when she reached London, she just handed over the manuscripts of her two new books to her publisher (Journal of a Residence in Chile during the Year 1822. And a Voyage from Chile to Brazil in 1823 and Journal of a Voyage to Brazil, and Residence There, During Part of the Years 1821, 1822, 1823, illustrated by herself), collected suitable educational material, and returned to Brazil in 1824. She stayed in the royal palace only until October of that year, when she was asked to leave due to courtiers' suspicion of her motives and methods (courtiers seem to have feared, with some justice, that she intended to Anglicize the princess Maria da Gloria). During her few months with the royal family, she developed a close friendship with the empress, Archduchess Maria Leopoldina of Austria, who passionately shared her interests in the natural sciences. After leaving the palace, Maria Graham experienced further difficulties in arranging for her transport home; unwillingly, she remained in Brazil until 1825, when she finally managed to arrange a passport and passage to England. Her treatment by palace courtiers left her with ambivalent feelings about Brazil and its government; she later recorded her version of events in her unpublished manuscript "Memoir of the Life of Don Pedro".

In March 1826, King João VI of Portugal died. His son Pedro inherited the throne, but preferred to remain Emperor of Brazil, so he abdicated the Portuguese throne in favour of his six-year-old daughter after two months. So, Maria Graham’s little chubby pupil suddenly became Maria II, Queen of Portugal.

Having arrived in London, Maria Graham took rooms in Kensington Gravel Pits, just south of Notting Hill Gate, which was something of an artists’ enclave. There lived the Royal Academy painter Augustus Wall Callcott and his musician brother John Wall Callcott, but also painters like John Linnell, David Wilkie and William Mulready, and musicians such as William Crotch (the first principal of the Royal Academy of Music) and William Horsley (John Callcott’s son-in-law). In addition, this closely-knit group was frequently visited by artists like John Varley, Edwin Landseer, John Constable and J.M.W. Turner.

Maria’s lodgings very quickly became a focal point for London’s intellectuals, such as the Scottish poet Thomas Campbell, Maria’s book publisher John Murray and the historian Francis Palgrave, but her keen interest and knowledge of painting (she was a skilled illustrator of her own books, and had written the book about Poussin) made it inevitable that she would quickly become part of the artists’ enclave as well.

It must have been love at first sight when Maria Graham and Augustus Callcott met, because they married on his 48th birthday, 20 February 1827. They immediately left for a year-long honeymoon to Italy, Germany, Austria and Czechoslovakia. It was his first trip abroad, and he obviously enjoyed it. From then on he would travel extensively, both to Europe and the Middle East, with Maria as well as with friends like Turner.

In 1831, during a trip in Italy, Maria Callcott ruptured a blood vessel and became an invalid. She could no longer travel, but she could continue to entertain her friends, and could continue her writing.

After her return from Brazil in 1825, her publisher, John Murray, had asked her to create a book about the famous and recently completed voyage of HMS Blonde to the Sandwich Islands (as Hawaii was then known). King Kamehameha II of Hawaii and his Queen Kamamalu had been on a visit to London in 1824, when they both died of the measles, against which they had no immunity. HMS Blonde was commissioned by the British Government to return their bodies to the Hawaiian Islands, with George Anson Byron, a cousin of the poet Byron, in command. The resulting book contained a history of the exotic royal couple's unfortunate visit to London, a résumé of the discovery of the Hawaiian Islands and visits by British explorers, as well as the story about Blonde’s journey. Maria wrote it with the help of official papers and journals kept by the chaplain, R. Rowland Bloxam; there is also a short section based on the records of the naturalist Andrew Bloxam.

In 1828, immediately after returning from their honeymoon, she published A Short History of Spain, and in 1835 her writings during her long convalescence resulted in the publication of two books; Description of the chapel of the Annunziata dell’Arena; or Giotto’s Chapel in Padua, and her first and most famous book for children; Little Arthur’s History of England, which has been reprinted numerous times since then (already in 1851 the 16th edition was published, and it was last reprinted in 1975). Little Arthur was followed in 1836 by a French version; Histoire de France du petit Louis.

In the mid 1830s her description of the earthquake in Chile of 1822 started a heated debate in the Geological Society, where she was caught in the middle of a fight between two rivalling schools of thought regarding earthquakes and their role in mountain building. Besides describing the earthquake in her Journal of a Residence in Chile, she had also written about it in more detail in a letter to Henry Warburton, who was one of the Geological Society’s founding fathers. As this was one of the first detailed eyewitness accounts by "a learned person" of an earthquake, he found it interesting enough to publish in Transactions of the Geological Society of London in 1823.

One of her observations had been that of large areas of land rising from the sea, and in 1830 that observation was included in the groundbreaking work The Principles of Geology by the geologist Charles Lyell, as evidence in support of his theory that mountains were formed by volcanoes and earthquakes. Four years later the president of the Society, George Bellas Greenough, decided to attack Lyell’s theories. But instead of attacking Lyell directly, he did it by publicly ridiculing Maria Callcott’s observations.

Maria Callcott, however, was not someone who accepted ridicule. Her husband and her brother offered to duel Greenough, but she said, according to her nephew John Callcott Horsley, "Be quiet, both of you, I am quite capable of fighting my own battles, and intend to do it". She went on to publish a crushing reply to Greenough, and was shortly thereafter backed by none other than Charles Darwin, who had observed the same land rising during Chile’s earthquake in 1835, aboard the Beagle.

In 1837 Augustus Callcott was knighted, Maria thus becoming Lady Callcott. But shortly afterwards her health began to deteriorate, and in 1842 she died, 57 years old. She continued to write until the very end, and her last book was A Scripture Herbal, an illustrated collection of tidbits and anecdotes about plants and trees mentioned in the Bible, which was published the same year she died.

Augustus Callcott died two years later, at the age of 65, having been made Surveyor of the Queen's Pictures in 1843.

In recognition of her services to Chile, as being one of the first persons to write about the young nation in the English language, the Chilean government paid for the restoration of Maria and Augustus Callcott’s joint grave in Kensal Green Cemetery in London in 2008.

The restoration was finalised with a commemorative plaque, unveiled by the Chilean ambassador to the United Kingdom, Rafael Moreno, at a ceremony on 4 September 2008. The plaque names Maria Callcott "a friend of the nation of Chile".