He is known for his contributions to the flora of the American Southwest and work on breeding cotton. His 1951 book Arizona Flora, co-authored with Thomas H. Kearney, and republished posthumously in 1960, is recognized as the most comprehensive study of Arizona plants of its time. Peebles named and described over 180 species or variety of plants, often in collaboration with Kearney.
Peebles and Kearney also collaborated on cotton breeding, and their contributions to the science of cotton growing have been recognized as "among the most outstanding of all time." In 1955, Peebles was awarded an honorary Doctorate of Science from the University of Arizona in recognition of his contributions to Arizona agriculture.
Peebles died at the age of 55 in March of 1956, the same year in which Kearney died. He was posthumously awarded the Superior Service award and medal by the United States Department of Agriculture. The cactus Pediocactus peeblesianus is named in his honor.