Clifford Prevost Grayson painted chiefly marine themes. He was a graduate of the Pennsylvania Academy of Fine Arts and studied at the Ecole des Beaux-Arts in Paris. His instructors included Thomas Eakins and Gerome and Bonnet, in Paris.
He was known for paintings that depicted individuals who were waiting for the return of loved ones gone to sea; particularly women, often quite distressed and anguished. He was an award winning artist and his work received acclaim in his own time. He was the recipient of the gold medal for a figure painting awarded by the Pennsylvania Academy of Fine Arts.
Clifford Prevost Grayson also worked as a teacher of the arts and was a member of several professional organizations. During 1877 - 1878 he was a member of the Sketch Club. He served as the Chairman of the Jury at the Pennsylvania Academy of Fine Art.
Grayson was involved in two controversies that involved a former teacher. During the year in which he chaired the jury at The Pennsylvania Academy, Eakins' painting was rejected after being determined that it had been displayed at the event previously. When Eakins was dismissed for taking the loincloth off a model at Drexel Institute, Grayson headed the art department.