She studied at the Tyler School of Art in Philadelphia and began her graphic design career as a record cover art director at both Atlantic and CBS Records in the 1970s. In 1984 she co-founded Koppel & Scher with friend Terry Koppel, and in 1991 she joined the Pentagram design consultancy as a partner.
Scher has been inducted into the Art Directors Club Hall of Fame (1998), received the Chrysler Design Award for Innovation in Design (2000), and a Gold Medal from the American Institute of Graphic Arts (2001). Some of her work is in the permanent collection of the Museum of Modern Art and the Cooper-Hewitt, National Design Museum. Her album designs have earned her four Grammy Award nominations.
As an artist she is known for her large-scale paintings of maps, covered with dense hand-painted labelling and information. She was involved in the planning of a new multi-use "urban center" in the Mount Vernon Square neighborhood of Washington D.C., and teaches at the School of Visual Arts in New York. She has been married to fellow designer Seymour Chwast since 1989.