[12] During the 1870s, Holmes gained a national reputation as a scientific illustrator, cartographer, pioneering archaeologist, and geologist.

[14] In the field, Holmes worked closely with the photographer William H. Jackson and back in Washington he helped produce Hayden's great achievement, the Geological and Geographical Atlas of Colorado, And Portions of Adjacent Territory (1877, 1881).

He was also a noted mountain climber, and a peak in Yellowstone National Park — Mount Holmes — was named in his honor.

In 1875, Holmes began studying the remains of the Ancestral Pueblo culture in the San Juan River region of Utah.

He expanded these studies to include textiles, and he became well known as an expert in both ancient and existing arts produced by Native Americans of the Southwest.

He left Washington temporarily, from 1894 to 1897, to serve as curator of anthropology at the Field Columbian Museum in Chicago, during which time he led an expedition to Mexico.

During this period he studied the Etowah Indian Mounds of the Mississippian culture in Georgia, and in 1903, he published his Synthesis of Pottery.

[18] Holmes lived with his son in Royal Oak, Michigan, upon his retirement in 1932 from the position of Director of the National Gallery of Art.

[20] In the year of his death, a memorial exhibition of ninety-two of Holmes' artworks was held at the Corcoran Gallery of Art.