In the mid-1970s, Ron Burgundy (Will Ferrell) is the famous anchorman for a local San Diego television station, fictional KVWN channel 4. He works alongside his friends on the news team: lead field reporter Brian Fantana (Paul Rudd), sportscaster Champ Kind (David Koechner), and intellectually disabled chief meteorologist Brick Tamland (Steve Carell). Station director Ed Harken (Fred Willard) notifies the team that they have maintained their long-held status as the highest-rated news program in San Diego, leading them to throw a wild party, where Ron unsuccessfully tries to pick up a beautiful, blonde woman (Christina Applegate). Ed later informs the team that they have been forced to hire Veronica Corningstone, the same woman whom Ron tried to pick up. After a series of inept attempts by the team to seduce her, she finally relents and consents to a "professional tour" of the city with Ron, culminating in a sexual relationship. Despite agreeing to keep the relationship discreet, Ron announces it on air.
After a dispute with a motorcyclist (Jack Black) involving Ron's dog, Baxter, being punted off the San Diego–Coronado Bridge, Ron is late to work. Veronica fills in for him on-air, and the couple break up. Veronica is made co-anchor, to the disgust of the team, and the two co-anchors become fierce rivals, both on and off the air. Depressed, the news team decides to buy new suits, but Brick, who was leading the way, gets them lost in a shady part of town. Confronted by competitor Wes Mantooth (Vince Vaughn) and his news team, Ron challenges them to a fight. However, when several other news teams converge on the site, a full-on melee ensues, broken up only by police sirens. Realizing that having a woman as a co-anchor is hurting their reputation, Ron gets in another heated argument with Veronica, and they get in a physical fight after she insults his hair, increasing tensions even more.
One of Veronica's co-workers tells her that Ron will read anything written on the teleprompter, so she sneaks into the station and changes the text. The next day, Ron—oblivious to what he is saying—concludes his broadcast with, "Go fuck yourself, San Diego!", instead of his usual closing line, "You stay classy, San Diego!" which subsequently provokes an angry mob outside the studio, and Ed has to fire Ron. Realizing she went too far, Veronica tries apologizing, but Ron angrily dismisses her. Ron becomes unemployed, friendless, and heavily antagonized by the public. Meanwhile, Veronica enjoys fame, although her male co-workers hate her. Ed tells Champ, Brick, and Brian that they may not talk to Ron or they will be fired. When a panda is about to give birth, all the news teams in San Diego head to the zoo to cover the story. In an attempt to sabotage her, a rival news anchor (Tim Robbins) pushes Veronica into a Kodiak bear enclosure. When Ed cannot find Veronica, he recruits Ron. Once at the zoo, Ron jumps in the bear pen to save Veronica, as the public watches helplessly. The news team then jumps in to save Ron. Just as a bear is about to attack, Baxter, who miraculously survived, appears and convinces the bear to spare them. As the group climbs out of the pit, Wes Mantooth appears and holds the ladder over the bear pit, threatening to drop Ron in, and tells him that deep down, he has always hated him, but suddenly pulls Ron to safety as he also respects him.
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 married with 11 children and is a top political adviser to George W. Bush, Champ is a commentator for the NFL before getting fired after being accused by Terry Bradshaw of sexual harassment, and Ron and Veronica are co-anchors for the CNN-esque World News Center.