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Ramis was born on November 21, 1944, in Chicago, Illinois, the son of Ruth (nee Cokee) and Nathan Ramis, who owned the Ace Food & Liquor Mart on the city's far North Side. Ramis had a Jewish upbringing. In his adult life, he did not practice any religion. He graduated from Stephen K. Hayt Elementary School in June 1958 and Nicholas Senn High School in 1962, both Chicago public schools, and in 1966 from Washington University in St. Louis, Missouri, where he was a member of the Alpha Xi chapter of Zeta Beta Tau fraternity.

Ramis began writing parodic plays in college, saying years later, "In my heart, I felt I was a combination of Groucho and Harpo Marx, of Groucho using his wit as a weapon against the upper classes, and of Harpo's antic charm and the fact that he was oddly sexy--he grabs women, pulls their skirts off, and gets away with it". He avoided the Vietnam War military draft by taking methamphetamine to fail his draft physical.  Following his work in St. Louis, Ramis returned to Chicago, where by 1968, he was a substitute teacher at schools serving the inner-city Robert Taylor Homes. He also became associated with the guerrilla television collective TVTV, headed by his college friend Michael Shamberg, and wrote freelance for the Chicago Daily News. "Michael Shamberg, right out of college, had started freelancing for newspapers and got on as a stringer for a local paper, and I thought, 'Well, if Michael can do that, I can do that.' I wrote a spec piece and submitted it to the Chicago Daily News, the Arts & Leisure section, and they started giving me assignments [for] entertainment features." Additionally, Ramis had begun studying and performing with Chicago's Second City improvisational comedy troupe.  Ramis' newspaper writing led to his becoming joke editor at Playboy magazine. "I called ... just cold and said I had written several pieces freelance and did they have any openings. And they happened to have their entry-level job, party jokes editor, open. He liked my stuff and he gave me a stack of jokes that readers had sent in and asked me to rewrite them. I had been in Second City in the workshops already and Michael Shamberg and I had written comedy shows in college". Ramis was eventually promoted to associate editor.
Harold Ramis