Walter and Margaret Keane were struggling artists when they met in Berkeley, California in 1953. Walter was recently divorced and Margaret’s marriage was unraveling. The two eventually married in 1955, but it wasn’t until 1957 when their work was shown at an outdoor art show in Washington Square Park in New York. The paintings that got the most attention - focusing on small girls with enormous eyes - became unusually popular throughout the late 1950s and early 1960s. Walter Keane claimed credit for the paintings and went to great lengths to promote them, becoming one of the most financially successful contemporary artists in America.

Walter and Margaret separated in 1964, and six years later, Margaret publicly revealed that she was the real artist behind those paintings. Walter denied Margaret's public revelation, forcing Margaret to sue Walter over the artist's rights to the paintings. Margaret eventually won her case by swifly drafting a sketch of a girl with big eyes, proving that she, and not Walter, was the true artist of the paintings.  For the next three decades until his death in 2000, Walter Keane insisted that he was the real artist even though he never provided any convincing evidence.

Decades later, screenwriters Scott Alexander and Larry Karaszewski came up with the idea for Big Eyes when they stumbled upon an entry on the Keanes in The Encyclopedia of Bad Taste.