Born in Plainfield, New Jersey, Hand began his animation career working on the Out of the Inkwell cartoons throughout the 1920s. He joined the Disney studio in 1930, during a major drive by Disney to recruit from the cream of animating talent. Hand immediately made his mark as an animator, contributing to mostly to Silly Symphonies such as Midnight in a Toy Shop, The China Plate and Egyptian Melodies. By 1932 he was regarded as one of Disney's top animators. as well as having become a close friend of Walt Disney. Hand's organizational skills made Disney select him to be the studio's third director after Burt Gillett and Wilfred Jackson. He made his directorial debut for the company with the Mickey Mouse short Building a Building, and went on to direct both Silly Symphony and Mickey Mouse shorts, including The Flying Mouse, Who Killed Cock Robin?, Three Orphan Kittens and Thru the Mirror. By the late 1930s Hand's management skills had allowed him to ascend in the hierarchy of the Studio to functioning as Disney's right-hand man. But as historian Michael Barrier notes "Hand's position was fundamentally untenable—he was second in command in an organization whose leader, younger than Hand himself, had no intention of ever stepping aside or sharing real power."
After leaving Disney in 1944, Hand went to England and for J. Arthur Rank established Gaumont British Animation at Moor Hall in 1946 to produce the Animaland and Musical Paintbox cartoon series. When these were unable to get distribution in the United States, the studio closed in 1950 and Hand moved to Colorado where he worked for the next 18 years at the Alexander Film Company, a maker of commercials and industrial films. The closure also put an end to the studio's plans to produce two animated features adapted from H. G. Wells' "The First Men in the Moon" and Lewis Carroll's "The Hunting of the Snark" as well. Hand's son David Hale Hand has formed David Hand Productions which owns the rights to the 19 Gaumont animated shorts and hopes to produce new films starring some of the characters in the shorts. In 1994, Hand was inducted into the Disney Legends program.