Bearing the unfortunate distinction of being whisked away from his home planet, Duckworld, a sentient, anthropomorphic duck named Howard suddenly finds himself tumbling through the vast cosmos. He crash-lands on Earth, smack-dab in the bustling city of Cleveland, Ohio. Disoriented and trying to make heads or tails of this alien world, Howard encounters an eclectic assortment of Earth's residents, both kind and nefarious. His arrival is not entirely misbegotten, though, as it leads him to an unexpected friendship with Beverly, a spirited and compassionate singer for a band who takes him under her wing.

As Howard adjusts to the quirks of human society, his presence garners the attention of some less-than-friendly Earthlings and eventually ties him into a larger, more ominous plot involving interdimensional travel. Alongside Beverly, Howard gets entangled with a pair of offbeat scientists—Phil, an enthusiastic but bumbling lab assistant, and Dr. Walter Jenning, whose involvement with an esoteric experiment known as the "laser spectroscope" inadvertently brought Howard to Earth. While grappling with the calamity of being trapped in a world he never made, Howard must confront dangers he never imagined in a bid to return to his own universe—even as some come to question whether the Earth might hold a new destiny for him.