During the 16th century, the CKCS was popular among the nobility in England. The people of the time believed that these dogs could keep fleas away, and some even believed that they could prevent forms of stomach illnesses. These dogs were sometimes called the "Spaniel Gentle" or "Comforter", as ladies taking a carriage ride would take a spaniel on their laps to keep them warm during the winter. Charles I kept a spaniel named Rogue while residing at Carisbrooke Castle; however, it is with Charles II that this breed is closely associated and it was said of him that "His Majesty was seldom seen without his little dogs".There is a myth that he even issued an edict that no spaniels of this type could be denied entry to any public place including Parliament. He preferred playing with his cavaliers rather than taking care of important matters.
During the reign of King William III and Queen Mary II, the long nosed style of spaniel went out of fashion. The Pug was the favoured dog at the time in the Netherlands, and with William's Dutch origin, they became popular in England too. At this time interbreeding may have occurred with the Pug, as the King Charles took on some Pug-like characteristics.

After the kings death, the Duke of Marlborough took over the breed. During the early part of the 18th century, John Churchill, 1st Duke of Marlborough kept red and white King Charles type spaniels for hunting. The duke recorded that they were able to keep up with a trotting horse. His estate was named Blenheim in honour of his victory at the Battle of Blenheim. Because of this influence, the red and white variety of the King Charles Spaniel and thus the Cavalier King Charles Spaniel became known as the Blenheim.
In 1926, American Roswell Eldridge offered a dog show class prize of twenty-five pounds each as a prize for the best male and females of "Blenheim Spaniels of the old type, as shown in pictures of Charles II of England's time, long face, no stop, flat skull, not inclined to be domed, with spot in centre of skull." The breeders of the era were appalled, although several entered what they considered to be sub-par King Charles Spaniels in the competition. Eldridge died before seeing his plan come to fruition, but several breeders believed in what he said and in 1928 the first Cavalier club was formed. The first standard was created, based on a dog named "Ann's Son" owned by Mostyn Walker, and the The Kennel Club recognized the breed as "King Charles Spaniels, Cavalier type".
World War II caused a drastic setback to the breed, with the vast majority of breeding stock destroyed because of the hardship. For instance, in the Ttiweh Cavalier Kennel, the population of sixty dropped to three during the 1940s. Following the war, just six dogs would be the starting block from which all Cavaliers descend. These dogs were Ann's Son, his litter brother Wizbang Timothy, Carlo of Ttiweh, Duce of Braemore, Kobba of Kuranda and Aristide of Ttiweh. The numbers increased gradually, and in 1945 The Kennel Club first recognized the breed in its own right as the CKC Spaniel.
The history of the breed in America is relatively recent. The first recorded Cavalier living in the United States was brought from the United Kingdom in 1956 by W. Lyon Brown, together with Elizabeth Spalding and other enthusiasts, she founded the Cavalier King Charles Club USA which continues to the present day. In 1994, the American Cavalier King Charles Spaniel Club was created by a group of breeders to apply for recognition by the American Kennel Club. The Cavalier would go on to be recognized in 1997, and the ACKCSC became the parent club for Cavaliers.