Through his Yale contacts and Spencer Baird of the Smithsonian Institution, he was selected as mineralogist and geologist of the Pacific Railroad Exploring Expedition of 1853, exploring a railroad route in southern California. He with Lt. John G Parke identified the San Gorgonio Pass as the best railroad route to the coast, which it became with the building of the Southern Pacific railroad twenty-four years later. More importantly to geologists, Blake saw the erosive power of wind-blown sand in the pass and contributed to the significant scientific debates about mountain building. Biographer David B. Dill, Jr. calls the exploration of the pass one of Blake's "crowning events" in a "long professional career rich in scientific and human values." Besides identifying geologic features along the route and exploring the mining fields of California, he was author of several of the Railroad Survey reports, which included his polished field sketches that are now sought after as works of art.