Picasso's painting was shocking even to his closest artist friends both for its content and for its formal experimentation. The subject matter of nude women was not in itself unusual, but the fact that Picasso painted the women as prostitutes in aggressively sexual postures was novel. Their blatant sexuality was heightened by Picasso's influence from non-Western art that is most evident in the faces of three of the women, which are rendered as mask-like, suggesting that their sexuality is not just aggressive, but also primitive. The unusual formal elements of the painting were also part of its shock value. Picasso abandoned the Renaissance illusion of three-dimensionality, instead presenting a radically flattened picture plane that is broken up into geometric shards. For instance, the body of the standing woman in the center is composed of angles and sharp edges. Both the cloth wrapped around her lower body and her body itself are given the same amount of attention as the negative space around them as if all are in the foreground and all are equally important.

The painting was widely thought to be immoral when it was finally exhibited in public in 1916. Braque is one of the few artists who studied it intently in 1907, leading directly to his later collaboration with Picasso. Because it predicted some of the characteristics of Cubism, Les Desmoiselles is considered proto or pre-Cubist.