He published his illustrations in Life magazine and other major national publications for more than 30 years, becoming editor in 1918 and later owner of the general interest magazine.

Gibson was born in Roxbury, Massachusetts on September 14, 1867. He was a son of Josephine Elizabeth (née Lovett) and Charles DeWolf Gibson. He had five siblings  and was a descendant of U.S. Senators James DeWolf and William Bradford.

A talented youth with an early interest in art, Gibson was enrolled by his parents in New York City's Art Students League, where he studied for two years.

Peddling his pen-and-ink sketches, Gibson sold his first work in 1886 to Life magazine, founded by John Ames Mitchell and Andrew Miller. It featured general interest articles, humor, illustrations, and cartoons. His works appeared weekly in the popular national magazine for more than 30 years. He quickly built a wider reputation, with his drawings being featured in all the major New York publications, including Harper's Weekly, Scribners and Collier's. His illustrated books include the 1898 editions of Anthony Hope's The Prisoner of Zenda and its sequel Rupert of Hentzau as well as Richard Harding Davis' Gallegher and Other Stories.

It is an oft-repeated urban legend that Gibson's wife and her elegant Langhorne sisters inspired his famous Gibson Girls, who became iconic images in early 20th-century society. The truth is that the first Gibson Girl appeared in 1890, more than two years before Gibson ever met the Langhorne family, and in later years it became fashionable for many of Gibson's friends and family to model for his illustrations. Their dynamic and resourceful father Chiswell Langhorne had his wealth severely reduced by the Civil War, but by the late 19th century, he had rebuilt his fortune on tobacco auctioneering and the railroad industry.

After the death of John Ames Mitchell in 1918, Gibson became editor of Life and later took over as owner of the magazine. As the popularity of the Gibson Girl faded after World War I, Gibson took to working in oils for his own pleasure. In 1918, he was elected into the National Academy of Design as an Associate member, and became a full Academician in 1932.

He retired in 1936, the same year Scribner's published his biography, Portrait of an Era as Drawn by C. D. Gibson: A Biography by Fairfax Downey. At the time of his death in 1944, he was considered "the most celebrated pen-and-ink artist of his time as well as a painter applauded by the critics of his later work."

On November 7, 1895, Gibson was married to Irene Langhorne (1873–1956), a daughter of railroad industrialist Chiswell Langhorne. Irene was born in Danville, Virginia, and was one of five sisters, all noted for their beauty, including Nancy Astor, Viscountess Astor, the first woman to serve as a Member of Parliament (MP) in the House of Commons of the United Kingdom. Irene and Charles were the parents of two children:

• Irene Langhorne Gibson (1897–1973), who married George Browne Post III (1890–1952), a grandson of architect George B. Post, in 1916. They divorced and she married real estate developer John Josiah Emery (1898–1976) in 1926.
• Langhorne Gibson (1899–1982), who married Marion Taylor (1902–1960) in 1922. He later married Parthenia Burke Ross (1911–1998) in 1936.

For part of his career, Gibson lived in New Rochelle, New York, a popular art colony among actors, writers and artists of the period. The community was most well known for its unprecedented number of prominent American illustrators. Gibson also owned an island off Islesboro, Maine which came to be known as 700 Acre Island; he and his wife spent an increasing amount of time there through the years.

Gibson died of a heart ailment in 1944, aged 77, at 127 East 73rd Street, his home in New York City. After a private funeral service at the Gibson home in New York, he was interred at Mount Auburn Cemetery in Cambridge, Massachusetts. His widow died at her home in Greenwood, Virginia in April 1956 at the age of 83.

Almost unrestricted merchandising saw his distinctive sketches appear in many forms. The Gibson cocktail has been claimed to be named after him, as it is said he favored ordering gin martinis with a pickled onion garnish in place of the traditional olive or lemon zest.

The Gibson Girl was the personification of the feminine ideal of physical attractiveness as portrayed by the pen-and-ink illustrations of artist Charles Dana Gibson during a 20-year period that spanned the late 19th and early 20th centuries in the United States. The artist saw his creation as representing the composite of "thousands of American girls".

The Gibson Girl image that appeared in the 1890s combined elements of older American images of contemporary female beauty, such as the "fragile lady" and the "voluptuous woman". From the "fragile lady" she took the basic slender lines, and a sense of respectability. From the "voluptuous woman" she took a large bust and hips, but was not vulgar or lewd, as previous images of women with large busts and hips had been depicted. From this combination emerged the Gibson Girl, who was tall and slender, yet with ample bosom, hips and buttocks. She had an exaggerated S-curve torso shape achieved by wearing a swan-bill corset. Images of her epitomized the late 19th- and early 20th-century Western preoccupation with youthful features and ephemeral beauty. Her neck was thin and her hair piled high upon her head in the contemporary bouffant, pompadour, and chignon ("waterfall of curls") fashions. The statuesque, narrow-waisted ideal feminine figure was portrayed as being at ease and stylish.

She was a member of upper middle class society, always perfectly dressed in the latest fashionable attire appropriate for the place and time of day. The Gibson Girl was also one of the new, more athletic-shaped women, who could be found cycling through Central Park, often exercised and was emancipated to the extent that she could enter the workplace. In addition to the Gibson Girl's refined beauty, in spirit, she was calm, independent and confident, and sought personal fulfillment. She could be depicted attending college and vying for a good mate, but she would never have participated in the suffrage movement.

Taking part in the suffrage movement was something more associated with the New Woman, another cultural image of women that emerged around the same time as the Gibson Girl. As a more popular version of the New Woman, the Gibson Girl both undermined and sanctioned some women's desires for progressive sociopolitical change. The New Woman was the more disconcerting of the two images at the time as she was seen as an example of change and disruption within the old patterns of social order, asking for the right to equal educational and work opportunities as well as progressive reform, sexual freedom and suffrage. Whilst the Gibson Girl took on many characteristics of the New Woman, she did so without involving herself in politics and thus did not appear to contemporaries at the time to be usurping traditionally masculine roles as the New Woman was deemed to. She therefore managed to stay within the boundaries of feminine roles without too much transgression.

Gibson depicted her as an equal and sometimes teasing companion to men. She was also sexually dominant, for example, literally examining comical little men under a magnifying glass, or, in a breezy manner, crushing them under her feet. Next to the beauty of a Gibson Girl, men often appeared as simpletons or bumblers; and even men with handsome physiques or great wealth alone could not provide satisfaction to her. Gibson illustrated men so captivated by her looks that they would follow her anywhere, attempting to fulfill any desire, even if it was absurd. One memorable drawing shows dumbstruck men following a Gibson Girl's command to plant a young, leafless tree upside-down, roots in the air, simply because she wanted it that way. Most often, a Gibson Girl appeared single and uncommitted. However, a romance always relieved her boredom. Once married, she was shown deeply frustrated if romantic love had disappeared from her life, but satisfied if socializing with girlfriends or happy when doting on her infant child. In drawings such as these there was no hint at pushing the boundaries of women's roles; instead they often cemented the long-standing beliefs held by many from the old social orders, rarely depicting the Gibson Girl as taking part in any activity that could be seen as out of the ordinary for a woman.

The artist believed that the Gibson Girl represented the beauty of American women:

I'll tell you how I got what you have called the 'Gibson Girl.' I saw her on the streets, I saw her at the theatres, I saw her in the churches. I saw her everywhere and doing everything. I saw her idling on Fifth Avenue and at work behind the counters of the stores ... I haven't really created a distinctive type, the nation made the type. What Zangwill calls the 'Melting Pot of Races' has resulted in a certain character; why should it not also have turned out a certain type of face? ... There isn't any 'Gibson Girl,' but there are many thousands of American girls, and for that let us all thank God.

Gibson believed that America's women would become more beautiful:

They are beyond question the loveliest of all their sex ... In the United States, of course, where natural selection has been going on, as elsewhere, and where, much more than elsewhere, that has been a great variety to choose from. The eventual American woman will be even more beautiful than the woman of to-day. Her claims to that distinction will result from a fine combination of the best points of all those many races which have helped to make our population.

Many women posed for Gibson Girl-style illustrations, including Gibson's wife, Irene Langhorne, who may have been the original model, and was a sister of Viscountess Nancy (Langhorne) Astor. Other models included Mabel Normand, Evelyn Nesbit, Minnie Clark, and Clara B. Fayette. The most famous Gibson Girl was probably the American-British stage actress, Camille Clifford, whose high coiffure and long, elegant gowns that wrapped around her hourglass figure and tightly corseted wasp waist defined the style.

Among the many "Gibson Girl" illustrators were Howard Chandler Christy whose work celebrating American "beauties" was similar to Gibson's, and Harry G. Peter, who was most famous for his art on Wonder Woman comics.

In the newly developing art of cinema, although most leading actresses were at the cutting style of the day, the ones who came to embody it best were the Biograph girls, Florence Lawrence and to a more ingénue side of it, Mary Pickford. They personified and catapulted the cult of the ideal woman for the masses beyond American borders. Camille Clifford, a woman known as the "ideal Gibson Girl", posed for various photographers and produced photographs that exemplified the physical characteristics of the Gibson Girl.

Some people argue that the Gibson Girl was the first national beauty standard for American women. Gibson's fictional images of her published in newspapers and magazines during the Belle Époque were extremely popular. Merchandise bearing her image included saucers, ashtrays, tablecloths, pillow covers, chair covers, souvenir spoons, screens, fans, and umbrella stands

By the outbreak of World War I, changing fashions caused the Gibson Girl to fall out of favor as women favored practical clothing compatible with changing times over the elegant dresses, bustle gowns, shirtwaists, and terraced, floor-length skirts favored by the Gibson Girl.   The image was not forgotten, however, with the USAAF World War II-era SCR-578, and the similar post-war AN/CRT-3, survival radio transmitters carried by aircraft on over-water operations being given the nickname "Gibson Girl" because of their "hourglass" shape, which allowed them to be held stationary between the legs while the generator handle was turned.