The painting depicts an antelope skull half submerged in sand. The skull occupies the left third of the landscape and is the one vertical element in an otherwise horizonal landscape. The landscape and sky, devoid of detail, are represented solely by four bands of different colour. The pallet takes inspiration from the New Mexico desert landscape and is predominantly in soft shades of brown, pink, and grey. Georgia O'Keeffe typifies the American Modernism style that dominated American art between the two World Wars. Modernism is characterized by abstraction and minimalism, and a rejection of historicism. Antelope embodies these qualities of the genre. The starkness of the antelope skull and its vertical orientation gives it an abstract architectural presence. Minimalism can be seen in the simplified rendering of the antelope horns set against the pale horizontal bands.

Paring down the details of the horizontal and vertical lines, and allowing the lines to dominate the composition, gives the painting a stability. Indeed, the composition is so stable as to be static, which is appropriate given the content. Also, the stability provides the cohesion and coherence characteristic of Modernism. Rejection of historicism is shown in the elimination in any detail that could indicate a point in history. Instead, O’Keeffe paints the timeless and almost eventless desert. The painting may represent timelessness, but it clearly identifies a geographic region. Her New Mexico series partakes of the increasing interest of American Modernists in regionalism and a new understanding the nation. In fact, the architectural rendering of the skull and horns can be considered an example of precisionism, which celebrated modern skyscrapers and a bright new future for America.

Arguably, O'Keeffe is best known for her middle 1920s flower paintings. “Antelope” retains some qualities of her earlier period with the large-scale and simplified depictions of natural forms. The curvilinear lines of the skull are reminiscent of, for example, Red Canna, painted in 1924. In both paintings, the microscopic examination of single natural forms, such as a flower or animal skull, removes the attachments of the mundane world and leaves the viewer alone with their thoughts. The vibrant saturated hues of the flower paintings and curving lines evokes an emotional response. Painted 30 years later, Antelope has an equal strength, but the palette and composition have replaced emotion with serenity.