Guerrero spent time as an undercard wrestler in the company, which was soon rebranded World Wrestling Entertainment, before becoming a trainer for WWE's second Tough Enough competition. Soon after returning to the active roster, Guerrero was aligned with his uncle Eddie, forming the tag team Los Guerreros. In contrast to his previous WCW storyline with his uncle, Guerrero fully adopted his uncle's policy of "Lie, Cheat and Steal" to win matches as part of the gimmick. The duo won the WWE Tag Team Championship twice, feuding with such teams as Edge and Rey Mysterio and Team Angle.
The tag team eventually turned into fan favorites and as Eddie's popularity grew, he began seeking the WWE Championship. In one angle, his uncle's singles title ambitions made Guerrero jealous and Guerrero turned on Eddie, broke from the team, and became a villain again. He was soon joined by his father Chavo Sr. who sided with his son instead of his brother. Eddie defeated Guerrero at the 2004 Royal Rumble.
After the feud with Eddie finished, Guerrero became a wrestler in the cruiserweight division and captured the WWE Cruiserweight Championship on several occasions.
On an August 26, 2004 episode of SmackDown!, Guerrero suffered a legitimate concussion due to Billy Kidman's shooting star press and had to be taken to the hospital. Guerrero returned several months later as a fan favorite again, exacting revenge from Kidman, who had turned into a villain as a result of the injury to Guerrero, but shortly returned to his villainous persona after receiving a villain reaction after facing then-cruiserweight champion Funaki in a losing effort during a SmackDown! show in Japan.
Guerrero went on to become Cruiserweight Champion once again at No Way Out in 2005 after eliminating Paul London in a six-way cruiserweight gauntlet match. He would lose the title to London in a battle royal a few weeks later; Guerrero was the first person eliminated from the battle royal when everyone else in the match ganged up to throw him out right at the beginning. In reality, Guerrero was forced to drop the title due to a broken orbital bone that would sideline him for several weeks.
On June 30, 2005, Guerrero became one of the last minute trades in the 2005 WWE Draft, which saw him jump from SmackDown! to the Raw brand. The next week, on Raw, he denounced his Hispanic heritage in favor of the Anglo-American way. This came after two weeks of being battered by the Mexican faction, The Mexicools. It led to the changing of his persona to "Kerwin White", a stereotypical, middle-class, white, Anglo-American man. He dyed his hair blond and often drove a golf cart to the ring which held his golf clubs. His new catch phrase became the pun, "If it's not White, it's not right." The phrase later changed to "If it's not Kerwin White, it's not right" because the original sounded racist. It was later be phased out entirely. Soon after his debut, White started making suggestive remarks towards African Americans, specifically directed towards then-babyface, Shelton Benjamin. On an episode of Raw, White cost Shelton a match against Rob Conway. Benjamin defeated White by disqualification the following week when Kerwin attacked Shelton with his golf club. At Unforgiven, White was beaten by Benjamin. White then hired Nick Nemeth as his new "caddy" to help him in his matches.
On the morning of November 13, 2005, Guerrero checked into the same hotel as his uncle, Eddie, in Minneapolis, Minnesota. Guerrero was alerted by hotel security that Eddie did not respond to a wake-up call and after security opened the locked door to the room, Guerrero found his uncle, but as he said in his video tribute to Eddie, someone who he saw as "his brother", unconscious. Guerrero attempted CPR but Eddie was declared dead when paramedics arrived on the scene.
Later that afternoon, Guerrero appeared at a press conference with WWE Chairman Vince McMahon to address Eddie's death. They announced that both shows that week would be tributes to Eddie. These events resulted in Guerrero dropping the Kerwin White gimmick and wrestling under his real name as a fan favorite to continue the Guerrero legacy. Under his real name, he defeated John "Bradshaw" Layfield (JBL) on the November 18, 2005 episode of SmackDown!, using the "Three Amigos" triple suplexes and the Frog Splash in tribute to Eddie. He also used the cheating tactic of throwing a steel chair to an opponent who catches it (while laying down himself) as the referee turns around and disqualifies the opponent, which Eddie made famous.
A month later, on the February 24, 2006 edition of SmackDown!, Guerrero attacked Randy Orton with the Three Amigos and the frog splash when Orton began to insult Eddie, and talked about the heritage of the Guerreros. Guerrero was soon dragged out by security, but kept yelling to Orton "You forgot about the Guerreros - the greatest wrestling family!" and "You forgot me!". On the February 27, 2006 episode of Raw, Guerrero faced off against now-heel, Shelton Benjamin in a qualifying match for the Money in the Bank ladder match at WrestleMania 22. During the match, Orton interfered and hit Guerrero with the RKO. This allowed Shelton to get the pinfall victory. On the April 3, 2006 edition of Raw, Guerrero came out to address the crowd. He thanked the fans for all the support they had given him and his family and for keeping Eddie's spirit alive, but he expressed his disappointment in not having a title match at WrestleMania 22. He felt that night would become his WrestleMania and he was going to dedicate his match to his Eddie. He proceeded to challenge Shelton Benjamin for the WWE Intercontinental Championship, but ended up losing after he missed a Frog Splash, allowing Benjamin to connect with his T-Bone Suplex finisher. In a segment that aired on WWE Unlimited, an emotional Guerrero decided to quit WWE, in storyline, after believing he had let his family, Eddie, and the fans down and expressed his doubts about being a wrestler.
On May 13, 2006 Guerrero appeared at a SmackDown! house show in El Paso, TX, defeating then-heel, Finlay. Guerrero also appeared at Judgment Day to support Rey Mysterio. Guerrero would then support Mysterio for a few weeks on SmackDown!. At the Great American Bash, Guerrero interfered in Mysterio's World Heavyweight Championship match, ostensibly to help Mysterio. Guerrero turned into a villain once more, however, by hitting Mysterio with a steel chair, which allowed challenger King Booker to win the match. On the August 4, 2006 episode of SmackDown!, Guerrero accused Rey of using Eddie's name to succeed, claiming that Rey disrespected Eddie's memory. Guerrero went on to beat Mysterio at SummerSlam, after Vickie Guerrero accidentally knocked Mysterio off the top turnbuckle. On August 25, Vickie came down to the ring to apologize to Mysterio and Guerrero. Vickie ended up turning on Mysterio by hitting him in the back with a steel chair. The following week on SmackDown!, Vickie announced herself as Guerrero's new manager. Weeks later on October 8, 2006, Mysterio gained his revenge on Guerrero by defeating him in a Falls Count Anywhere match at No Mercy. Guerrero eventually challenged Mysterio to an "I Quit" match, in which Guerrero won after inflicting multiple chair shots to Rey Mysterio. As per the condition of the match, Mysterio was forced to leave SmackDown!, possibly ending the emotional feud between the two.
A week later, Chris Benoit, another old friend of Eddie's, tried talking to Vickie, but she would not hear it. It started a feud between Guerrero and Benoit and both men would have numerous confrontations over the following weeks. Benoit defeated Guerrero to retain the WWE United States Championship at the Survivor Series. After weeks of continued interaction, the two faced off in a United States title rematch at Armageddon that Guerrero also lost when he tapped out to a Sharpshooter. Guerrero got yet another rematch the following Friday, losing the match after Vickie hit Benoit with the title belt. Guerrero snapped after the match, knocking over Vickie and attacking Benoit. The feud concluded with Benoit forcing Guerrero to submit in a No-Disqualification match.
At No Way Out, Guerrero was labeled a surprise entrant in a Cruiserweight Open Match by the announcers (despite already having been advertised as one of the wrestlers in the match on WWE.com and on the No Way Out merchandise); he entered last and pinned Jimmy Wang Yang after a frog splash, thus winning the Cruiserweight Championship from Gregory Helms. On June 24, Guerrero retained his title against Jimmy Wang Yang at Vengeance: Night of Champions. He then retained his title on the June 29 edition of SmackDown! in a triple threat match that also involved Jamie Noble and Funaki, when he pinned Funaki after the Gory Bomb. At The Great American Bash, he lost the Cruiserweight title in a Cruiserweight open when Hornswoggle pinned Noble (Hornswoggle was not originally in the match but was in the ring when the bell rang, thus becoming an official entrant).
Guerrero then turned his attention to Rey Mysterio, whom he had put out of action, in storyline, in 2006. Before Mysterio's return at SummerSlam, Guerrero mocked Mysterio's knee injury and taunted him during matches. He was, however, unable to defeat Mysterio at the pay-per-view. He then lost an "I Quit" re-match to Mysterio, when Mysterio continued to assault Chavo's left knee with a steel chair, thus injuring him in storyline. This allowed Guerrero to have time off to serve his suspension for violating the WWE Wellness Policy.
Chavo remained inactive until the December 18, 2007 edition of ECW, where he appeared after the main event between WWE United States Champion Montel Vontavious Porter and ECW Champion CM Punk and proceeded to attack the vulnerable ECW Champion, sending a message that he wanted a title shot.With the beginning of 2008, Guerrero entered a feud with CM Punk regarding his ECW title. Guerrero challenged Punk to several matches until he finally won the third via countout after interference from World Heavyweight Champion Edge to earn a championship match. The previous matches he lost via countout and disqualification. On the January 22 edition of ECW, Guerrero defeated CM Punk in a No Disqualification match to win the ECW Championship following interference from Edge. In the process he proclaimed Edge and company as his "familia". He then successfully defended his title against CM Punk at No Way Out and on the March 4 episode of ECW, both times pinning Punk after a frog splash.At WrestleMania XXIV, Guerrero lost the ECW Championship to Kane in a record eight seconds. Shortly afterward, Bam Neely debuted to act as his bodyguard. Shortly after losing the ECW Championship, Guerrero had several attempts to regain the ECW Championship including losing to Kane at Backlash and also failing to become the number one contender at One Night Stand. Guerrero became involved in the Edge-Undertaker rivalry at this point, but Edge later turned on all La Familia teammates, including Guerrero. After this, Guerrero returned to singles and tag team action with Neely, feuding with ECW newcomers Evan Bourne and Ricky Ortiz, and also attempted to regain the ECW Championship at Unforgiven in a Championship Scramble match, but failed. He also was embroiled in the Undertaker-Big Show storyline, and lost a casket match to the Undertaker on October 31. After that he tried to win the ECW Championship from Matt Hardy, but he failed to win the title.Guerrero returned to the SmackDown brand until April 2009, where he was drafted to the Raw brand as part of the 2009 Supplemental Draft. He then became involved in the feud between Vickie Guerrero and Santina Marella, in which he attempted to help his aunt on numerous occasions. At Extreme Rules, Guerrero and his aunt faced Santina in a Hog Pen match, in which the duo lost. Upon Vickie's departure from WWE, Chavo continued to feud with Marella and defeated him on the June 18 edition of WWE Superstars As of late, Guerrero is in a feud with Hornswoggle, where the two constantly face off in various types of matches, with Hornswoggle coming out with an advantage and the win.