In the 1920s Buff developed close friendships with the modernist architects Rudolph Schindler and Richard Neutra, and the artist, Maynard Dixon. Undoubtedly, he shared a much greater aesthetic affinity with these artists than with most of his California contemporaries. He accompanied Dixon on painting trips through the desert Southwest, and executed two mural commissions with Dixon in the late 1920s.

In 1922, Buff married artist and museum curator, Mary Marsh. In 1936 they began collaborating on children's books which Mary wrote and Conrad illustrated. Nature and the environment, Native Americans, and Switzerland constituted the themes of most of the thirteen books they published together. Several were nominated for Newbery and Caldecott awards.

As Buff's work matured, it became increasingly abstract. Where he had once emphasized basic shapes in the landscape, he later came to exaggerate them to create two-dimensional patterns, rendered in increasingly bright and simple colors. Although he retained his pointillist technique, the strokes became much broader and, often, unconnected. He loved the clear air of the desert and, through color, attempted to capture its effects on the red rocks of his favorite places such as Zion, Monument Valley, and the Colorado River.