Uncle Tupelo was an alternative country music group from Belleville, Illinois, active between 1987 and 1994. Jay Farrar, Jeff Tweedy, and Mike Heidorn formed the band after the lead singer of their previous band, The Primitives, left to attend college. The trio recorded three albums for Rockville Records, before signing with Sire Records and expanding to a five-piece. Shortly after the release of the band's major label debut album Anodyne, Farrar announced his decision to leave the band due to a soured relationship with his co-songwriter Tweedy. Uncle Tupelo split on May 1, 1994, after completing a farewell tour. Following the breakup, Farrar formed Son Volt with Heidorn, while the remaining members continued as Wilco.

Although Uncle Tupelo broke up before it achieved commercial success, the band is renowned for its impact on the alternative country music scene. The group's first album, No Depression, became a byword for the genre and was widely influential. Uncle Tupelo's sound was unlike popular country music of the time, drawing inspiration from styles as diverse as the hardcore punk of Minutemen and the country instrumentation and harmony of the Carter Family and Hank Williams. Farrar and Tweedy's lyrics frequently referred to Middle America and the working class of Belleville.

Jay Farrar, along with his brothers Wade and Dade, played in an early 1980s garage band named The Plebes. Hailing from Belleville, Illinois, The Plebes sought to enter a battle-of-the-bands competition but needed another high school student as a member to perform. They invited Jeff Tweedy, a high school friend of Jay Farrar, to join the band and play with them for the show. Despite a lack of skill with his instrument, Tweedy played an important role in the band by booking early gigs. While The Plebes had been playing music in a rockabilly style, Tweedy wanted to play punk rock like the music that he originally heard the group perform. This caused tensions between Tweedy and Dade Farrar, who left the band two months after Tweedy joined.

Before leaving the band in 1984, Dade Farrar introduced its members to Mike Heidorn, the younger brother of his girlfriend; Heidorn then joined the group as their drummer. The Plebes then decided to change its name to The Primitives, a reference to a 1965 song by psychedelic rock group The Groupies. Due to the unpopularity of punk rock in the St. Louis area, The Primitives began to play blues-oriented garage rock at fast tempos. They performed regularly at a wedding hall in Millstadt, Illinois, where Tweedy's mother Jo Ann would collect the cover fee. They also performed regularly at B St Bar in Belleville with bands such as The Newsboys (later Sammy and the Snowmonkeys), Charlie Langrehr, and The Symptoms. Wade Farrar was the lead singer of the band, but his commitment to Southern Illinois University and an attempted enlistment in the United States Army meant he was only able to dedicate a small amount of time to the group. Additionally, Heidorn broke his collarbone during a concert in 1986, which caused the band to go on hiatus. Jay Farrar and Tweedy continued to write songs and perform at Heidorn's house while he recovered, and by 1987 they had restarted the group. The Primitives temporarily added Tony Mayr as a bassist so that Tweedy could play guitar, but a month later the band decided to keep Tweedy on bass and remain a three-piece. To avoid confusion with a successful British band also named The Primitives, they decided to change their name once again, to Uncle Tupelo. Although they performed only 1960s cover songs as The Primitives, the trio decided to take a new approach and write their own music under their new name.

The Primitives renamed themselves Uncle Tupelo, a name created by combining two randomly chosen words from the dictionary. Inspired by the name, cartoonist Chuck Wagner, a friend of the band, created a character resembling an old, fat Elvis Presley. The trio recorded a four-song demo tape, which got them supporting slots opening for headline artists such as Johnny Thunders and Warren Zevon. Tweedy met Tony Margherita while working as a clerk at Euclid Records in St. Louis. After attending two of the band's shows, Margherita offered to become their manager. Uncle Tupelo began to play regular shows at Cicero's Basement — a bar close to the campus of Washington University in St. Louis. Bands playing in a similar style, including Brian Henneman's group Chicken Truck, often played at the venue, which by late 1988 was considered the locus of a new music scene. The band temporarily expanded to a four-piece with the addition of the guitarist Alex Mutrux, but soon reverted to a trio.

Uncle Tupelo recorded demo tracks in the attic studio of future Chicago punk producer Matt Allison in Champaign, Illinois. The demo, distributed with the title Not Forever, Just for Now, includes "I Got Drunk" and "Screen Door", as well as early versions of several other songs that would appear on the band's first studio album. The CMJ New Music Report gave the tape a rave review, and called Uncle Tupelo the best unsigned band of the year. The accolade drew the attention of independent labels, and the band decided to sign with Jay Fialkov and Debbie Southwood-Smith of Giant Records, who offered to book them at CBGB in New York City. Explaining the decision, the band said that "[our] original goals don't get distorted with an independent label."

Shortly after Uncle Tupelo's signing, Giant Records changed its name to Rockville Records. The band's first album for Rockville, No Depression, was recorded over ten days in January 1990, at Fort Apache South recording studio in Boston, Massachusetts. The album's thematic structure revolved around their lives as adolescents in Belleville; examples are songs about wanting to avoid factory work and songs about fearing a potential Persian Gulf War military draft. Impressed by their previous work on Dinosaur Jr.'s Bug, the band wanted Paul Kolderie and Sean Slade to produce the album. Slade let Farrar play on the same 1961 Gibson Les Paul SG Junior that J. Mascis originally played on Bug. The album was released on June 21, 1990, and the band celebrated by playing at Cicero's for two nights.

In between tours, Farrar, Tweedy and Heidorn formed a country cover band named Coffee Creek, along with Brian Henneman (later a member of The Bottle Rockets). Henneman impressed Uncle Tupelo, and he was invited to be a guitar technician and occasional multi-instrumentalist for the band. While Farrar and Heidorn would avoid drinking too much after shows, Tweedy would continue drinking throughout the night. Although Tweedy stopped after he began dating Sue Miller in 1991, a significant communication gap had already been opened between Tweedy and Farrar.