After receiving her BS in Psychology from Colorado State University, Karen Margolis continued research in Neural Psychology while studying portraiture at the Art Student's League in New York City.  She furthered her studies in art at Parsons School of Design and the School of Visual Arts.  During a Microscopy course at John Jay College of Criminal Justice, through the New York Microscopical Society, Margolis was inspired to diverge from her investigations of figurative art in order to create work exploring universality of macro/micro patterns.

Residing in New York City, Margolis recently completed a public installation for Amtrak’s Metropolitan Lounge in Moynihan Train Hall, New York City. In 2023 she was also commissioned to create a sculpture series for a Science/Life complex in Boston. Margolis created a public art installation for the Art on Paper Fair in New York City, March 2020.  Her work was included in the "Cut up/Cut out" exhibition, traveling to museums throughout the country from 2016 through 2021.  Recent solo exhibitions include Foley Gallery, New York City, K. Imperial Fine Arts, San Francisco and Garis and Hahn in Los Angeles.  In 2018 Margolis completed a public art commission of mosaic panels for the MTA Arts in Transit at the 86 Street subway station, N Line in Brooklyn, NY.  Margolis' work has been exhibited in the Paper Biennial at the Rijswijk Museum in the Netherlands, Salon Zurcher, Paris, France and in collaboration with M Missoni, New York City, through Garis & Hahn Gallery. Prior exhibitions include Bridgewater University in Massachusetts, Rockland Center for the Arts, The Hunterdon Art Museum, The Aldrich Museum of Contemporary Art, The Parrish Art Museum, the Fine Arts Center of the University of Massachusetts in Amherst, Weatherspoon Art Museum and The Delaware Center for Contemporary Art. 

Margolis received a Pollock-Krasner Foundation Grant in 1998 and in 2000 designed a critically acclaimed set design for an Off-Broadway play.  That same year she received a workspace residency at Dieu Donne Papermill.  She was instrumental in creating the Dr. Seuss exhibit at the Children's Museum of Manhattan.  In 2004 she conceived and implemented a program to teach art to blind and visually impaired teenagers at The Lighthouse International.  In 2015 she worked as a consultant for Art Beyond Sight, coordinating with the Mayor's Office for People with Disabilities, Margolis organized and implemented special events for the 25th Anniversary of the Americans with Disabilities Act.