His earliest works were impressionistic, but after seeing the work exhibited by the Fauves in 1905, Braque adopted a Fauvist style. The Fauves, a group that included Henri Matisse and André Derain among others, used brilliant colors and loose structures of forms to capture the most intense emotional response. Braque worked most closely with the artists Raoul Dufy and Othon Friesz, who shared Braque's hometown of Le Havre, to develop a somewhat more subdued Fauvist style. In 1906, Braque traveled with Friesz to L'Estaque, to Antwerp, and home to Le Havre to paint.

In May 1907, he successfully exhibited works in the Fauve style in the Salon des Indépendants. The same year, Braque's style began a slow evolution as he came under the strong influence of Paul Cézanne, who died in 1906, and whose works were exhibited in Paris for the first time in a large scale, museum-like retrospective in September 1907. The 1907 Cézanne retrospective at the Salon d'Automne greatly impacted the direction that the avant-garde in Paris took, leading to the advent of Cubism.

Braque's paintings of 1908 – 1913 began to reflect his new interest in geometry and simultaneous perspective. He conducted an intense study of the effects of light and perspective and the technical means that painters use to represent these effects, appearing to question the most standard of artistic conventions. In his village scenes, for example, Braque frequently reduced an architectural structure to a geometric form approximating a cube, yet rendered its shading so that it looked both flat and three-dimensional by fragmenting the image. He showed this in the painting "House at L'estaque". In this way, Braque called attention to the very nature of visual illusion and artistic representation.

Beginning in 1909, Braque began to work closely with Pablo Picasso, who had been developing a similar approach to painting. At the time Pablo Picasso was influenced by Gauguin, Cézanne, African tribal masks and Iberian sculpture, while Braque was mostly interested in developing Cézanne's idea's of multiple perspectives. “A comparison of the works of Picasso and Braque during 1908 reveals that the effect of his encounter with Picasso was more to accelerate and intensify Braque’s exploration of Cézanne’s ideas, rather than to divert his thinking in any essential way.” The invention of Cubism was a joint effort between Picasso and Braque, then residents of Montmartre, Paris. These artists were the movement's main innovators. After meeting in October or November 1907, Braque and Picasso, in particular, began working on the development of Cubism in 1908. Both artists produced paintings of monochromatic color and complex patterns of faceted form, now called Analytic Cubism. A decisive moment in its development occurred during the summer of 1911, when Georges Braque and Pablo Picasso painted side by side in Céret, in the French Pyrenees, each artist producing paintings that are difficult — sometimes virtually impossible — to distinguish from those of the other. In 1912, they began to experiment with collage and papier collé. Their productive collaboration continued and they worked closely together until the outbreak of World War I in 1914 when Braque enlisted in the French Army, leaving Paris to fight in the First World War.

French art critic Louis Vauxcelles first used the term Cubism, or "bizarre cubiques", in 1908 after seeing a picture by Braque. He described it as 'full of little cubes', after which the term quickly gained wide use although the two creators did not initially adopt it. Art historian Ernst Gombrich described cubism as "the most radical attempt to stamp out ambiguity and to enforce one reading of the picture - that of a man-made construction, a colored canvas." The Cubist movement spread quickly throughout Paris and Europe.

Braque was severely wounded in the war, and when he resumed his artistic career in 1917 he moved away from the harsher abstraction of cubism. Working alone, he developed a more personal style, characterized by brilliant color and textured surfaces and — following his move to the Normandy seacoast — the reappearance of the human figure. He painted many still life subjects during this time, maintaining his emphasis on structure. During his recovery he became a close friend of the cubist artist Juan Gris.

However, he nonetheless continued to work throughout the remainder of his life, producing a considerable number of distinguished paintings, graphics, and sculptures, all imbued with a pervasive contemplative quality. Braque, along with Matisse, is credited for introducing Pablo Picasso to Fernand Mourlot, and most of the lithographs and book illustrations he himself created in the 1940s and '50s were produced at the Mourlot Studios. He died on 31 August 1963, in Paris. He is buried in the church cemetery in Saint-Marguerite-sur-Mer, Normandy, France. Braque's work is in most major museums throughout the world.

Braque believed that an artist experienced beauty "… in terms of volume, of line, of mass, of weight, and through that beauty [he] interpret[s] [his] subjective impression...” He described "objects shattered into fragments… [as] a way of getting closest to the object… Fragmentation helped me to establish space and movement in space”. He adopted a monochromatic and neutral color palette in the belief that such a palette would work simultaneously with the form, instead of interfering with the viewer's conception of space; and would focus, rather than distract, the viewer from the subject matter of the painting.

Although Braque began his career painting landscapes, in 1908, he, alongside Picasso, discovered the advantages of painting still lifes instead. Braque explained that he, “… began to concentrate on still-lifes, because in the still-life you have a tactile, I might almost say a manual space… This answered to the hankering I have always had to touch things and not merely see them… In tactile space you measure the distance separating you from the object, whereas in visual space you measure the distance separating things from each other. This is what led to, long ago, from landscape to still-life” A still-life was also more accessible, in relation to perspective, than landscape, and permitted the artist to see the multiple perspectives of the object. Braque's early interest in the still life reappeared in the 1930s.

During the period between the wars, Braque exhibited a looser and freer approach to Cubism, intensifying his color use and a looser rendering of objects. However, he still remained strongly committed to the cubist method of simultaneous perspective and fragmentation. In contrast to Picasso, who continuously reinvented his approach to painting, producing both representational and cubist images, and incorporating surrealist ideas into his work, Braque continued in the Cubist style, producing luminous, other-worldly still life and figure compositions. By the time of his death in 1963, he was regarded as one of the elder statesmen of the School of Paris, and of modern art.