On April 5, 1980 four college pals-Bill Berry, Peter Buck, Mike Mills and Michael Stipe-took the stage together for the first time to play at a friend's birthday party. The band they started that night stayed together for thirty years and changed the shape of rock music. R.E.M. By MTV tells R.E.M.'s story in their own words, through three decades of performances and interviews R.E.M gave to MTV channels in the USA and around the world. Featuring revealing, never-before-seen footage, R.E.M. By MTV tells the amazing story of a band that did it their own way, and changed how a generation of musicians after them did it, too.

To cash in on all of the "real world" hype of the events in the first film, a man from Burkitsville, Maryland opens a "Blair Witch Hunt" tour, which shows patrons various locations from the original film. A bunch of college students decide to take the tour, and wind up in Rustin Parr's house. There, they decide to camp for the evening, but in the morning, they realize they didn't sleep and they don't remember anything that happened the previous night. From there, they go back to town, and discover that something...or someone has come with them.

Tommy Brown and his friend Sincere are gangsters who have learned how to make a good living by dealing drugs and pulling armed robberies. Tommy and Sincere have been able to move out of the ghetto in Queens where they were raised and relocate to an upscale section of Manhattan; they would seem to have it made, but both realize that their lives are headed toward a dead end. Sincere begins getting in touch with his African roots and tries to convince his girlfriend Tionne that they should emigrate to the Motherland, while Tommy has a religious awakening and joins the Nation of Islam.