His thesis directly earned him the A. Cressey Morrison Prize in Natural History of the New York Academy of Sciences, and was published by the Geological Society of America as Special Paper 38 in 1942.

At the height of World War II, he was recruited to the United States Geological Survey to work on the wartime Strategic Minerals Program.

In 1943, he joined Virgil Barnes of the Texas Bureau of Economic Geology in the Ellenburger Project, studying the stratigraphy and sedimentology of this important early Paleozoic carbonate complex.

At UCSB he founded the Preston Cloud Research Laboratory, originally dedicated to paleomicrobiology and to studies of the first lunar geological samples from the Apollo 11 space mission.

[1][7] Cloud was a member of the National Academy of Sciences for thirty years, he was chairman of the Geology Section and occupied positions in its Council and Executive Committee.

He also gave the Hadean geologic eon, Earth's earliest, its name, using the Greek word for the Underworld to refer to a molten state of constant heat.

One of Cloud's scientific heirs, his nephew John P. Grotzinger, is the Project Scientist for the NASA Mars Science Laboratory Curiosity rover Mission Team.

University of California, Santa Barbara has a graduate student award named Preston Cloud Memorial Awards, which is given annually and carries minimum $200 for first-time attendance at a national or major meeting of a professional organization such as the Geological Society of America, American Geophysical Union, Association of American Petroleum Geologists, or for a student presenting a talk at such a meeting for the first time.

He postulated that adaptive radiation in any favourable ecological condition could always result in diversification of an original population into several distinct lineages, thus giving rise to eruptive evolution.

[2] Cloud was a noted public speaker and symposium participant on the subjects of resources, the human future, origin of life and the primitive earth, and he regularly delivered many popular lectures.

During his service in World War II, as D. L. Peck, Director of the U.S. Geological Survey, noted in a letter dated January 29, 1941: "[Preston Cloud] created quite a stir among the locals who suspected that this person of slight stature, emerging from holes in the ground, must certainly be a Japanese spy in their midst.” At 5'6", he would often put his desk and chairs on 4-inch-high raisers so that, as he claimed, he could look down on others to show his authority.

In Santa Barbara, Preston met and, in 1973, married Janice Gibson, an opera singer and mother of three children, Morgan, Dante, and Amanda.