In the mid 1970's, Ron Burgundy (Will Ferrell) is the famous and successful anchorman for San Diego's KVWN-TV Channel 4 Evening News. He works alongside his friends on the news team: fashion-oriented lead field reporter Brian Fantana (Paul Rudd), sportscaster Champion "Champ" Kind (David Koechner), and a "legally retarded" chief meteorologist Brick Tamland (Steve Carell). The team is notified by their boss, Ed Harken (Fred Willard), that their station has maintained its long-held status as the highest-rated news program in San Diego, leading them to throw a wild party. Ron sees an attractive blond woman and immediately tries to hit on her. After an awkward, failed pick-up attempt, the woman leaves.
The next day, Ed informs the team that he has been forced by the network to hire Veronica Corningstone (Christina Applegate), a female news reporter from Asheville, North Carolina and the same woman Ron had tried to pick up the night before. The news team attempts to seduce Veronica using various inept, arrogant and sexist methods, all of which backfire. Ron ends up asking her out under the guise of helping out a new co-worker, which she accepts. During their date, Ron woos Veronica by playing jazz flute in his friend Tino's (Fred Armisen) club. Veronica goes against her policy of not dating co-workers and sleeps with Ron. The next day, despite agreeing with Veronica to keep the relationship discreet, Ron tells the entire news room that he and Veronica are in a sexual relationship (and later announces it on the air).
The next day when Ron is on his way to the station, he throws a burrito out his car window, accidentally hitting a motorcyclist (Jack Black) in the head, causing him to crash. In a fit of rage, the biker retaliates by punting Ron's dog, Baxter, off a bridge. A distressed and incoherent Ron calls Brian from a pay phone and tells him what happened. Since Ron is now late, Brian frantically tells him to come to the station because Veronica is about to take his place. Despite Ron's efforts to arrive on time, Veronica goes on air. After Ron arrives, he has an argument with Veronica about the situation and they break up. The next day, Veronica is made co-anchor, much to the entire news team's disgust. The co-anchors soon become fierce rivals and argue with each other both on and off the air.
One day while feeling down on themselves, the News team decides to buy new suits. However on the way to the suit shop Brick, who was leading the way, gets them lost ending up in a shady part of town. They are then confronted by Wes Mantooth (Vince Vaughn) and the evening news team. Tired of their rudeness and petty anger, Ron challenges them to a fight. All armed with crude weapons the two teams are about to fight when they are joined by Channel 2 news team with lead anchor Frank Vitchard (Luke Wilson), the public news team and their lead anchor (Tim Robbins), and the Spanish language news with lead anchor Arturo Mendez (Ben Stiller). A full on melee ensues between the five teams until they all flee when police sirens are heard. When they return to the studio, Ron gets in another heated argument with Veronica and they get in a physical fight after she insults his hair, increasing tensions even more.
While in a restaurant celebrating Veronica's success, one of Veronica's co-workers tells her that Ron will read anything that is written on the teleprompter. Later, Veronica sneaks into the station and changes the words in Ron's teleprompter. The next day, instead of Ron saying his signature "You stay classy, San Diego!" closure, Ron ends the broadcast with, "Go f*** yourself, San Diego." Everyone in the studio, except Ron, is speechless. An angry mob gathers outside the studio and Ed is forced to fire Ron. Garth is especially hurt and sobs while labeling Ron "a poopmouth". Veronica sees that she has gone too far and attempts to apologize, but Ron angrily dismisses her while being led through the mob by security, yelling at her that she had "reduced him to rubble".
Three months later, Ron is unemployed, friendless, hated by the city, and is a slovenly drunk. In this time, Veronica has become very famous, but is hated by her male coworkers for sabotaging Ron; Ed told Champ, Brick, and Brian not to talk to Ron or he will fire them if they do. When it is announced that Ling-Wong the panda is about to give birth, all San Diego news teams head to the zoo to cover the story. In an attempt to sabotage her, the public news anchor pushes Veronica into a Kodiak bear enclosure. When Ed cannot find Veronica, he calls the bar where Ron spends most of his time and reluctantly asks him to return. Ron then summons the rest of his team by blowing the "News Horn", despite the fact that they were all standing a foot away playing pool. Baxter, who has miraculously survived, hears this call and follows the voice to find Ron. Once at the zoo, Ron jumps into the bear pen to save Veronica, with everyone else at the zoo watching. The Channel 4 news team then jumps in to help Ron. Just as the leader of the bears is about to rip Ron and Veronica apart, Baxter shows up and convinces the bear to let them live by mentioning that he is a friend of the bear's cousin, Katow-jo, whom he met in the wild.
After Ron and Veronica reconcile, it is shown that in years to come, Brian becomes the host of a Fox reality show named Intercourse Island, Brick is George W. Bush's top political adviser, Champ is a commentator for the NFL before he was fired for sexually harassing Terry Bradshaw, and Ron and Veronica are co-anchors for the CNN-esque World News Center, taking over after the narrator retires and it is shown to be some time later as Ron and Veronica are shown wearing 80's fashions.