The daughter of Russian émigrés, Pauline ("Pauly") Alpert D'Orlando grew up in Revere, Massachusetts and studied painting at the Massachusetts College of Art in Boston. After marrying Albert D'Orlando, a Unitarian minister, she moved with her husband to New Orleans in 1950. She began studying enameling on her own in New Orleans and, over time, it became her principal medium. Wanting to work on a scale larger than most commercial kilns could accommodate, she designed her own kiln which was subsequently constructed for her by Thompson Enamels. This larger kiln allowed her to produce individual panels of approximately 16 x 20 inches and even larger multi-part pieces. With a solid grounding in art, D'Orlando produced unusually painterly and richly colored enamels which depict idealized figures and dream-inspired landscapes. She also specialized in large-scale portraiture. She exhibited regularly at Naomi Marshall's Downtown Gallery in New Orleans and became a leading figure in the local art community. The Downtown Gallery also showed work by George Dureau, Ann Cooper, Noel Rockmore, John McCrady, and Leonard Flettrich.

When Pauly D'Orlando passed away in 1978, a scholarship was established in her honor to support Unitarian Universalist students pursuing a career in the visual arts.