After a series of singles wins, Guerrero faced Diamond Dallas Page after a short feud on Fall Brawl in a losing effort on September 15.

Eventually, Guerrero's treatment at the hands of Eddie would drive him "crazy," and he adopted the gimmick of a psycho fixated with a hobby horse he dubbed "Pepé.

[20] He was also a member of the comedy stable The Misfits in Action (MIA), consisting of himself, Hugh Morris (better known as Bill DeMott), Lash LeRoux and Van Hammer.

As Loco, he defeated Daffney for the Cruiserweight Championship in a triangle match also involving Disco Inferno on June 7, 2000 episode of Thunder.

[32] At No Way Out on February 15, Guerrero defeated Rey Mysterio to win the WWE Cruiserweight Championship, following interference from his father (now known as Chavo Classic).

In the following weeks, Guerrero defeated Mysterio, Funaki, Ultimo Dragon, Spike Dudley, Jamie Noble, Nunzio in one-on-one title matches.

On the August 26 episode of SmackDown!, Guerrero suffered a legitimate concussion due to Billy Kidman's shooting star press and had to be taken to the hospital.

[34] Shortly after his feud with Kidman ended, Guerrero returned to his heel persona after receiving a negative reaction while facing then-cruiserweight champion Funaki in a losing effort during a SmackDown!

He defeated John "Bradshaw" Layfield (JBL) on the November 18 episode of SmackDown!, using the "Three Amigos" triple suplexes and the Frog Splash in tribute to Eddie.

The referee then turned and, seeing the "unconscious" Guerrero, almost disqualified the oblivious, chair-wielding JBL but stopped short so the tribute-style match could continue.

[52] Guerrero, however, hit Mysterio with a steel chair, which allowed challenger King Booker to win the match and the title, turning heel once again.

After weeks of continued interaction, the two faced off in a United States Championship rematch at Armageddon on December 17 that Guerrero lost when he tapped out to a Sharpshooter.

On the July 9, 2010 episode of SmackDown, Guerrero competed in a triple threat Money in the Bank qualifying match, along with Ziggler and MVP.

His last match in WWE was teaming up with JTG and Young against Yoshi Tatsu, Conor O'Brian and Vladimir Kozlov on NXT in a losing effort.

[75] On July 16, Guerrero defeated El Sensacional Carlitos and Orlando Colón to win the WWC Caribbean Heavyweight Championship.

[83] He made his debut on July 26 episode of Impact Wrestling, aligning himself with Hernandez and beginning a short feud with Gunner and Kid Kash.

[85] The two subsequently set their sights on the TNA World Tag Team Championship, unsuccessfully challenging champions Bad Influence (Christopher Daniels and Kazarian) for the titles on September 6 episode of Impact Wrestling.

[88] Guerrero and Hernandez received their rematch for the titles on March 10 at Lockdown, but were again defeated by Aries and Roode in a three-way match, also involving Daniels and Kazarian.

[89] On following episode of Impact Wrestling, Guerrero and Hernandez were set for another shot at the titles, but the two were ambushed by the Aces & Eights before the match could start.

[90] The title match took place the following week, where Guerrero and Hernandez failed again to regain the TNA World Tag Team Championship, following interference from Daniels and Kazarian.

[91] On the next episode of Impact Wrestling, Guerrero and Hernandez defeated Daniels and Kazarian to earn another shot at the TNA World Tag Team Championship.

[92] Guerrero and Hernandez received their title shot on April 11 episode of Impact Wrestling, where they defeated Aries and Roode in a Two-out-of-Three Falls match, with the added stipulation that they would have to break up if they lost, to regain the TNA World Tag Team Championship.

[93] On June 2 at Slammiversary XI, Guerrero and Hernandez lost the TNA World Tag Team Championship to Gunner and James Storm in a fatal four-way elimination match, also involving Austin Aries and Bobby Roode and Bad Influence.

[99] On January 7, 2015, episode (taped October 5, 2014),[100] Guerrero participated in a 20-men Aztec Warfare battle royal to become the inaugural Lucha Underground Champion.

Guerrero returned to Lucha Underground on June 10 (taped March 22, 2015), defeating Blue Demon Jr.[102] On January 10, 2016, Guerrero won the vacant Gift of the Gods Championship in a match also involving Aero Star, El Siniestro de la Muerte, Joey Ryan, Sexy Star, Texano, and Willie Mack,[103] though he lost the championship a week later to Cage.

Guerrero returned in Aztec Warfare 4 on the season 4 premiere, entering at number 17 and making it to the final 3 before being eliminated by Pentagon Dark.

[104] During the second part of Ultima Lucha Cuatro, Chavo saved his cousin Shaul Guerrero from being assaulted by Famous B, turning him back into a face.

[111] Guerrero made his All Elite Wrestling debut on the July 21, 2021 episode of AEW Dynamite, where he was presented as the "executive consultant" for Andrade El Idolo.

He made an appearance as the fictional wrestler James Vazquez also known as El Mayordomo on the NBC TV series Grimm's fifth-season episode "Silence of the Slams".

Chris Benoit, Eddie Guerrero, and Brian Adams were also discovered to have been given steroids prior to their deaths during this investigation, as well as Sylvain Grenier.