O'Keeffe trained as a naturalist painter, but when she began to study the works of Arthur Wesley Dow, who was known for his emphasis on design and composition, her artwork became more abstract and modern. She was one of the first American artists to develop an abstract visual vocabulary with which to express herself. O'Keeffe said "I found I could say things with colors and shapes that I couldn't say any other way – things I had no words for," and in Pelvis Series, Red with Yellow she has taken the theme of animal bones, a motif of her work, and distilled it down to the thoughts she wanted to express.

Pelvis Series - Red with Yellow shows many of the hallmarks of O'Keeffe's work. The image of the pelvis bone is tightly cropped using the same composition techniques as were becoming popular at the time in photography. The animal bone becomes unrecognizable, instead the image is abstracted, resembling a dream-like almost Martian landscape. One of the first Modernists, O'Keeffe often used surprising cropping and point of view to create an image which is visually striking and intriguing, and this painting is one of the best examples of that.

While the oil painting is abstract, O'Keeffe's naturalist training is evident by the beautiful rendering of light and shade on the bone. Most of her Pelvis Series paintings, such as 1943's Pelvis with the Distance, depict the animal bones in their natural colors, here the bone is bathed in a rust-colored light as if at sunrise or sunset. Through the bone's socket we are shown a rich, golden yellow sky. The choice of color seems to be influenced by the vast New Mexico landscapes she painted in, indeed the shape of the pelvis bone with its curved hole resembles one of the weathered rocks around her Ghost Ranch home. Red with Yellow is one of the most famous of O'Keeffe's Pelvis Series, and one of the most visually striking.