Losing My Religion originated as a combination of ideas envisioned by Stipe and Singh. Stipe wanted the promo to be a straightforward performance video. Singh wanted to create a video in the style of a certain type of Indian filmmaking, where everything would be "melodramatic and wry dreamlike", according to Stipe.
The video begins with a brief sequence inside a dark room where water drips from an open window. Buck, Berry, and Mills run across the room while Stipe remains seated. A pitcher of milk drops from the windowsill and shatters, and the song begins. Singh drew inspiration from the Italian painter Caravaggio and Russian filmmaker Andrei Tarkovsky. The video is laden with religious imagery such as Saint Sebastian and Hindu deities, portrayed in a series of tableaus.
The video was nominated in nine categories at the 1991 MTV Video Music Awards. The video won six awards, including Video of the Year, Best Group Video, Breakthrough Video, Best Art Direction, Best Direction, and Best Editing.