Margo Grant Walsh was born Marjolaine Cleone Grant on December 12, 1936 in Poplar, Montana. Her mother, Ann McArthur Grant, was of Scottish descent, and her father Alfred Grant, was Chippewa. Walsh is an enrolled member of the Turtle Mountain Band of Chippewa. The family moved to Portland, Oregon during World War II. Walsh attended the University of Oregon, where she earned a Bachelor of Science degree from the School of Architecture and Allied Arts in 1959, and a Bachelor of Interior Architecture degree in 1960.

After graduating, she moved to San Francisco and soon began working at Skidmore, Owings & Merrill. During her time there, Walsh played a major role in the design and project management of several major projects, including the Tenneco building in Houston, Texas, Mauna Kea Beach Hotel in Waimea, Hawaii, Qantas Wentworth Hotel in Sydney, Australia, Bank of America headquarters in San Francisco, California, and Marine Midland Bank in Buffalo, New York.

In 1973, Art Gensler hired Walsh to manage the interior architecture design of Pennzoil Place in Houston, Texas. Gensler and Associates was a new firm based in San Francisco, and Art Gensler had to set up an office in Houston to manage the Pennzoil project. After the success of that project, Gensler made Walsh Vice President of the firm, and more projects quickly followed. They found a steady clientele of law offices and financial institutions and the firm grew rapidly. Walsh oversaw this expansion, playing a major role in the opening of regional offices in Washington, D.C., Boston, New York City, and London. Walsh relocated to New York City, where she has primarily resided since the late 1970s. In 1994, she married John P. Walsh at St. Patrick's Cathedral in New York City, and they enjoyed 4 years of marriage before John passed away in 1998 due to cancer.

Major Gensler clients that Walsh worked with include Goldman Sachs, JPMorgan Chase, Mobil Oil, Credit Suisse First Bank, and Christie's, as well as several prestigious law firms, including Clifford Chance, Cadwalader, Wickersham & Taft, Cravath, Swaine & Moore, King & Spalding, Linklaters, and Shearman & Sterling. Walsh served as Vice Chairman and Managing Principal of Gensler for many years, retiring in 2004 after over 40 years in the business of interior architecture.

Margo Grant Walsh has been widely honored for her contributions to the field of Interior Architecture. She was inducted into the Interior Design Magazine Hall of Fame in 1987 and the University of Oregon Business Hall of Fame in 2008. She received a Distinguished Service Award for Interior Architecture from Rhode Island School of Design in 2000, the Leadership Award from the International Interior Design Association New York Chapter in 2000, the Ellis F. Lawrence Medal from the School of Architecture and Allied Arts at the University of Oregon in 2002, and the Legend Award from Contract Magazine in 2002, among other accolades. She has also done many lectures, presentations, and speaking engagements about her life and career, with a special interest in inspiring and mentoring women in the field.

Walsh started collecting silver beginning in the 1980s. Her frequent travel for work lent itself to connecting with dealers and artisans all over the world, and she eventually amassed over 800 of pieces of antique silver with a primary focus on 20th century silver and metalwork. She has put on major exhibitions of her collection at several museums, including Portland Art Museum, the Museum of Fine Arts, Houston, Jordan Schnitzer Museum of Art, and SFO Museum at San Francisco International Airport. Walsh also collected and exhibited over 300 footstools from the 18th to early 20th century. In 2008, she published a catalog chronicling her silver collection in collaboration with the Museum of Fine Arts, Houston titled "Collecting by Design: Silver and Metalwork from the Twentieth Century from the Margo Grant Walsh Collection." In 2017, she was honored with the Gertrude Bass Warner Award by the Jordan Schnitzer Museum of Art. Recent exhibitions include "A New Woman: Clara Barck Welles, Inspiration & Influence in Arts & Crafts Silver," which originally opened at Jordan Schnitzer Musum of Art in 2021, then moved to the SFO Museum in June of 2023, and "The First Metal: Arts & Crafts Copper" at Jordan Schnitzer Museum of Art, which opened in May of 2023.