Harris Glenn Milstead, (who preferred being called by his middle name to distinguish him from his father) was born on October 19, 1945, in Baltimore, Maryland to Harris Bernard and Frances Milstead. Glenn was an only child, his mother having suffered two miscarriages prior to his birth. By 1945, his family was relatively well-off within their community and were socially conservative Baptists. Glenn would later describe his family as "your upper middle-class American family."

By the age of 12, Glenn and his parents moved to Lutherville, Maryland, a suburb of Baltimore. He attended Towson High School where he was bullied for being overweight and his perceived effeminacy. In a 1988 interview he recounts how the bullies in his school beat him badly on a daily basis. He kept this to himself for fear that things would only get worse until one day, when he had to go to the doctor for a physical, his bruises were noticed after he disrobed. After breaking down and speaking up about the abuse he was going through at school his parents called the authorities and the vicious kids were expelled. Sadly this only made Glenn more unpopular in his school. Glenn was a very introverted and artistic teenager who loved painting and took an interest in horticulture who suffered so much from being self conscious about his weight that, in the same interview mentioned above, he speaks of how he never went out until he was about sixteen years old - around the time he met and became friends with future filmmaker John Waters - and even then he always wore a raincoat to cover himself. He learned how superficial the world can be when, in his junior year, he finally went on a diet and lost eighty pounds and suddenly, people who wouldn't speak to him before, suddenly started talking to him and he was able to make friends. He describes that experience as a "rude awakening at a very young age."

After graduating high school in 1963, Glenn began attending the Marinella Beauty School, where he learned hair styling which would benefit him in his career in show business. After graduating he worked at several different salons and in time his parents helped him buy his own salon in Townson hoping he would learn responsibility. He would later quit hairdressing in 1970.

A couple of the friends Glenn began collecting throughout the years were filmmaker John Waters and David Lochary who would appear in several movies with Glenn/Divine later. Glenn and his friends easily embraced the counterculture and underground elements of Baltimore, frequenting the beatnik bars and clubs of the time. The nickname "Divine" was given to Glenn by Waters himself. At the time, Waters was reading Our Lady of the Flowers by Jean Genet which was a controversial book about homosexuals living on the outskirts of Parisian society. Waters borrowed the name "Divine" from a character in the book. In a 1973 quote Divine confirmed that he liked the name John had given him and that pretty much no one called him Glenn anymore.

It was in the 1970s, while frequenting LGBT events and after Divine made his name known, that Waters would encourage Divine to make his drag persona more outrageous and gaudy, commenting that Divine should become the "Godzilla of drag queens" which was in direct contrast with the beauty and glamour normally associated with drag queens.