Born in Illinois, Sarah Blakeslee studied as a teenager at the Art Institute of Chicago and the Corcoran School of Art in Washington DC. She enrolled in the Pennsylvania Academy of the Fine Arts after high school. Shortly after graduating from the Academy, she married the painter Francis Speight. The couple lived in Bucks County until 1961, when Speight took a position at East Carolina College, precipitating a move to North Carolina. She remained there teaching and painting until 1998 when she returned to Philadelphia to be near her daughter Elizabeth.

Blakeslee exhibited at the Art Institute of Chicago and the Corcoran Gallery of Art; was a regular exhibitor at the Pennsylvania Academy of the Fine Arts until 1964; showed work at the North Carolina Museum of Art; and exhibited at the Golden Gate International Exposition at the 1939 World's Fair. The Works Progress Administration employed her to paint a mural for the Strasburg Virginia Post Office which is still on view there.

Her works are in the collections of the Greenville Museum of Art, North Carolina Museum of Art, Pennsylvania Academy of the Fine Arts, The Johnson Collection, National Academy of Design, and the Cameron Art Museum among others.