When Punk returned to ROH, he wrestled ROH World Champion Samoa Joe for the championship in a three match series. The first match between the two was held on June 12, 2004 at "World Title Classic" in Dayton, Ohio. The match would end in a 60-minute time limit draw when neither Punk nor Joe were able to pin or cause the other to submit within the time limit given. The second match was supposed to be held on December 4, 2004 but because of Steve Corino being pulled from a match with Joe by Pro Wrestling ZERO-ONE, it was rescheduled to be held on October 11, 2004 for October 16 in Punk's hometown of Chicago. At the event titled "Joe vs. Punk II" on October 16, Punk and Joe fought to another 60-minute time limit draw. "Joe vs. Punk II" became Ring of Honor's best-selling DVD at the time and the match between Punk and Joe was also given a five-star rating by Dave Meltzer's Wrestling Observer Newsletter. The series ended after Joe defeated Punk in their third and final match on December 4, 2004 at "All-Star Extravaganza 2" where there was no time limit.
Punk started in the WWE's developmental territory Ohio Valley Wrestling and debuted on September 8, 2005 in a six-man tag team dark match where he teamed with Nigel McGuinness and Paul Burchill in a losing effort to the team of Deuce Shade, Elijah Burke and Seth Skyfire. On November 9, 2005, Punk defeated Ken Doane to become the OVW Television Champion. Brent Albright was supposed to face Doane but lost his chance when Punk hit him with a steel chair. This led to Punk feuding with Albright. On January 4, 2006, Punk was involved in a Three-Way Dance match with both Doane and Albright. He lost the championship when Punk submitted to Albright's finishing move, the Crowbar. The feud ended on February 1, 2006 when a double turn occurred. Albright turned heel by allowing the Spirit Squad to beat Punk which turned Punk face. During John Cena's WrestleMania 22 entrance, Punk made a small appearance as a gangster and rode on the side of a 1930s era car to the ring.
Matt Cappotelli, the OVW Heavyweight Champion at the time, vacated the championship in February 2006 after he found out that he had a brain tumor. After Cappotelli vacated the title, OVW held a tournament to crown a new champion. Punk was able to reach the finals and faced Brent Albright. Albright defeated Punk in the finals to become the new champion. Punk and Albright feuded again and Punk was able to defeat Albright in a strap match on May 3, 2006 to become the champion. He also became one-half of the Southern Tag Team Champions when he teamed with Seth Skyfire and defeated Shad Gaspard and the Neighborhoodie at a house show on July 28, 2006. They lost the championships to Deuce Shade and "Domino" Cliff Compton on July 28, 2006 and Punk feuded with Skyfire. Skyfire was supposed to face Punk in a match for the OVW Heavyweight Championship but he was attacked before the match by Charles "The Hammer" Evans. Chet Jablonski replaced Skyfire in the match and defeated Punk to win the championship. After Punk lost the championship, he was called up to WWE's main roster full-time.
Punk debuted in the WWE on the ECW brand in a match against Justin Credible on August 01, 2006. He made his televised debut on the July 4 episode of "ECW on Sci Fi". During his debut, he cut a short pre-taped promo where he talked about his straight edge lifestyle. His first televised match was on August 1, 2006 at the Hammerstein Ballroom where he defeated Justin Credible. During his time there, he started a winning streak. He started a feud with Mike Knox over Knox's girlfriend, Kelly Kelly. Punk was able to qualify for the Extreme Elimination Chamber at December to Dismember after he defeated Knox in their first match. He competed in the Survivor Series match where he teamed with D-Generation X and the Hardy Boyz to defeat Rated-RKO, Knox, John Morrison and Gregory Helms. During the Chamber match, Punk was the first person eliminated by Rob Van Dam.
He then began a feud with Hardcore Holly. On January 9, 2007, Holly was able to snap Punk's six-month unbeaten streak after he defeated him. When his feud with Holly was over, Punk started a feud with Matt Striker. Striker defeated Punk which gave Punk a second loss on his record. Punk defeated Johnny Nitro and earned a chance to compete in the Money in the Bank ladder match at WrestleMania 23. Punk didn't win the match though as it was won by Mr. Kennedy.
Punk turned heel by joining the New Breed alliance on the April 10, 2007 "ECW on Sci Fi". He turned face again two weeks later when he kicked the New Breed's leader Elijah Burke in the head and cost them a four on four elimination match. Punk delivered his finishing move, the Go To Sleep, to Burke and sarcastically apologized before he left the ring. Punk would defeat Burke in a singles match at Judgment Day and teamed with The ECW Originals (Tommy Dreamer and The Sandman) to defeat The New Breed (Elijah Burke, Matt Striker and Marcus Cor Von) in a six-man tag team tables match at One Night Stand.
When then-ECW Champion Bobby Lashley was drafted to "Raw", he was stripped of the championship and ECW held a tournament to decide the new champion. Punk defeated Marcus Cor Von on the June 19 episode of "ECW on Sci Fi". Punk was supposed to face Chris Benoit at next but Benoit legitimately no-showed the event after he killed his family and himself. He was replaced by Johnny Nitro and Nitro defeated Punk for the vacant championship.
Punk was able to challenge for the title again at The Great American Bash against Nitro (who changed his ring name to John Morrison at this point) but was again defeated by Morrison. Punk challenged Elijah Burke and Tommy Dreamer in a triple threat match. The match was to determine who the next competitor in Morrison's 15 Minutes of Fame Challenge, in which Punk won. Punk was able to defeat Morrison a week later for an ECW Championship title match at SummerSlam. Morrison defeated Punk at SummerSlam when Morrison used the ropes for a leverage pin.
During the September 1, 2007 (aired September 4) ECW taping, Punk was able to defeat Morrison in a "last chance" title match to win the ECW Championship. Punk successfully defended his championship against Elijah Burke at Unforgiven, Big Daddy V via disqualification at No Mercy, The Miz at Cyber Sunday, John Morrison on the November 6, 2007 episode of "ECW", and in a triple threat match against The Miz and John Morrison at Survivor Series. On the January 22, 2008 episode of ECW, Punk was defeated by Chavo Guerrero for the ECW Championship in a No Disqualification match after Edge ran in and speared Punk. At WrestleMania XXIV, he competed in the Money in the Bank ladder match and defeated Chris Jericho, Montel Vontavious Porter, Shelton Benjamin, John Morrison, Mr. Kennedy and Carlito.
On the June 23, 2008 episode of "Raw", Punk was drafted to the Raw brand during the 2008 WWE Draft. During his first night on "Raw", Batista beat down the World Heavyweight Champion Edge and left him lying in the ring. Punk then ran down the ramp to the ring with referee Mike Chioda. He then cashed in his Money in the Bank contract, hit Edge with the Go to Sleep and pinned him to become the new World Heavyweight Champion. Punk defended the title for the first time later in the night against JBL. Punk was able to hold the championship until Unforgiven on September 7, 2008. Before Punk was able to compete in the Championship Scramble match, he was attacked by The Legacy (Randy Orton, Cody Rhodes and Ted DiBiase with Manu). Orton ended the attack by punting Punk in the head. This led to Punk being unable to compete in the match and having to forfeit the title. In the match, Punk was replaced by Chris Jericho, who was able to win the match and the title. Punk had a rematch against Jericho eight days later on the September 15 episode of "Raw" but he was unable to regain the title in a steel cage match.