In 1928 he married. He worked first as a federal prosecutor, and then he started a lucrative Wall Street practice, leaving it for an appointment as a special prosecutor with the title, "Chief Assistant US Attorney for the Southern District of New York. In 1935, he was appointed a special prosecutor in New York County. He was tasked to aggressively pursue the mob, organized racketeering, and political corruption, including Tammany Hall leaders known for ties to gangsters.
On multiple occasions he had the opportunity to bring notorious gangster Dutch Schultz to trial, after the second trial, Schultz proposed to assassinate Dewey. New York crime boss Lucky Luciano, and the "Mafia Commission" decided that this would cause an all-out crackdown on their activities, and instead had Schultz Killed. Dewey then turned his attention to Luciano, and eventually won the conviction of Luciano for a prostitution racket, obtaining a sentence of 30 to 50 years for Luciano.
in 1937, Dewey was elected District Attorney of New York County (Manhattan), and obtained national celebrity, being nicknamed, the "Gangbuster." He even served as an inspiration for a number of dramas, including radio serials and movies.
In 1938, Dewey ran for Governor of New York, and lost. He rang again in 1942, winning with a large plurality. As governor he cut taxes, doubled state aid to education, increased salaries for state employees, and reduced the state's debt by over $100 Million. He also signed the first state law that prohibited racial discrimination in employment.
In 1940, Dewey sought the Republican presidential nomination. He lost the nomination, being considered too young (at 38) and inexperienced to lead the nation in war time. He was also criticized for being against intervention in Europe. He ran again in 1944, gaining the republican nomination. His campaing was noted for crusading against inefficiencies, corruption and communist influences, but avoided military and foreign policy debates. He was the first candidate for president born in the 20th Century, and to date the youngest Republican Presidential nominee. Dewey lost the election by the narrowest margin of any candidate that had run against FDR.
In 1948, Dewey Ran for president for the last time, and was widely considered a shoe-in. It was so widely predicted that the Chicago Daily Tribune famously printed "DEWEY DEFEATS TRUMAN" as it's post-election headline, before the returns were conclusively in. Those returns showed that Harry S Truman had won.
Dewey remained Governor of New York until his 3rd term expired, retiring from public service, and returning to his law firm, Dewey Ballantine.
On March 16, 1971, Dewey died from a massive heart attack while on vacation in Miami. He and his wife are buried in the town cemetery of Pawling, New York, near his beloved Farm since 1938, Dapplemere, (now called Dewey Lane Farm).
Dewey is memorialised by the New York State Thruway having been renamed for him in 1964, and an award named for him by the New York City Bar Association, which was first awarded on November 29, 2005