Goodis was born in Philadelphia, Pennsylvania, the oldest child of William Goodis and Mollie Halpern Goodis. William Goodis was a Russian-Jewish émigré born in 1882 who had arrived in America with his mother in 1890. David Goodis's mother, Mollie Halpern, was born in Pennsylvania also into a family of Russian-Jewish émigrés. In Philadelphia, Goodis's father co-owned a newspaper dealership and later went into the textile business as the William Goodis Company. A brother, Jerome, born in 1920, died of meningitis at age three. In 1922, another brother, Herbert, was born into the family.
Goodis attended Simon Gratz High School and was engaged in student affairs, editing the school newspaper, serving as student council president, and participating in athletics as a member of both the track and swim teams. He also had the distinction of being chosen valedictorian for the graduating class of 1935, delivering a speech entitled "Youth Looks at Peace". As a college student, he continued and expanded on the interests he had pursued as a high school student, contributing to the student newspaper as both writer and cartoonist. It was during this period that he purportedly tried his hand at novel writing with a book titled Ignited. The novel was never published, and no copy of it has been discovered. Goodis later claimed: "The title was prophetic. Eventually, I threw it into the furnace." Goodis graduated from Temple University in 1938 with a degree in journalism.
While working at an advertising agency, Goodis started writing his first published novel, Retreat from Oblivion. After it was published by Dutton in 1939, Goodis moved to New York City, where he wrote under several pseudonyms for pulp magazines, including Battle Birds, Daredevil Aces, Dime Mystery, Horror Stories, Terror Tales and Western Tales, sometimes churning out 10,000 words a day. The first pulp story published under his own name, titled "Mistress of the White Slave King", appeared in Gangland Detective Stories (November 1939). Over a five-and-a-half-year period, according to some sources, he produced five million words for the pulp magazines. While the quantity of his output far eclipses that of his predecessors Dashiell Hammett and Raymond Chandler, unlike theirs, the vast majority of his pulp stories have never been reprinted.

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