America’s third Secretary Commerce, Herbert Hoover, is the most distinguished by a longshot:
Hoover was born in 1874 in Iowa and oprhaned at age 9 after which time he lived with a grandfather and two uncles before entering Stanford University in 1891 as part of their first class. After graduation, Hoover worked in the mining industry in Australia, then China (where he and his wife are said to have learned Mandarin), then Australia again, and then as a mining consultant on a global basis. When the First World War broke out, he put his Quaker instincts for humanitarianism to good use and helped organize the orderly evacuation of American citizens from the war-affected countries. Success in that role pushed him to the creation of the Committee for Relief in Belgium which brought food and humanitarian aid to that semi-occupied nation. When the United States entered the war, Woodrow Wilson appointed him head of the American Food Administration and after the war he continued doing humanitarian work in Europe both through the American Relief Administration and the American Friends Service Committee.
In light of his broad popularity and non-political persona, there were efforts made to recruit him as a Democratic candidate for the presidency in 1920. Instead, Hoover revealed that he was a Republican—albeit of the progressive bent and a Theodore Roosevelt supporter in the 1912 presidential three-way—and tried to get support in the California GOP primary. He lost, and down went his short-term presidential ambitions.
Nevertheless, when Warren Harding became president he offered Hoover either the Commerce Department or the Secretary of the Interior job. Hoover took Commerce, believing he could turn the thus-far-undistinguished cabinet post into a kind of national economic policymaking hub. It’s a matter of some dispute how much policy impact he wound up having at the end of the day, but as Secretary he energetically promoted public-private partnerships, tried to help spread the gospel of business efficiency, and was an early promoter of the car-centric brand of urbanism that would come to define the country after the war. This, combined with his earlier humanitarian work, was good enough to leave him as a kind of national symbol of prosperity, can-do spirit, and the idea that a business orientation wasn’t antithetical to the general welfare. He resigned his post as Harding’s term [UPDATE: Should be Coolidge's term, Harding was dead] was nearing its end, captured the GOP nomination, and badly beat Al Smith in the 1928 general election.