Glackens was born of humble means. Early on, he supported himself as an illustrator and reporter by day and took drawing classes at night at the Pennsylvania Academy of the Fine Arts. The mentorship of Robert Henri led Glackens (and other illustrators) to painting and, around the turn of the century, to New York. There the group of mostly Philadelphia artists formed the so-called Ashcan School, known for their scenes of city life. Glackens had attended Central High School in Philadelphia with Albert C. Barnes, and the two men remained lifelong friends. Glackens recommended and sometimes purchased Impressionist and modernist paintings for Barnes, and many of these are anchoring paintings in the galleries of the Barnes Foundation today.
Glackens married Edith Dimock, an heiress (and painter) from Hartford, Connecticut. The couple lived the high life, with a magnificent Manhattan townhouse, summers on Long Island, and trips to Europe.