Murdoch signed a deal with World Wrestling Entertainment in July, 2005. On August 22, 2005, a promo was shown showcasing his debut along with the returning Lance Cade. Cade played a smooth-talking cowboy, while Murdoch appeared to be an angry "white trash" southern trucker.
Cade and Murdoch won their debut match on the September 5, 2005 episode of Raw. They defeated World Tag Team Champions Hurricane and Rosey in a non-title match, earning themselves a title match at Unforgiven. During the match, Murdoch delivered an elevated DDT on The Hurricane to the outside, causing The Hurricane to suffer a stinger. This allowed Cade and Murdoch to win the World Tag Team Championship. They would eventually lose their title at Taboo Tuesday to Big Show and Kane.
On November 28, during his match against Shelton Benjamin, commentator Joey Styles acknowledged that Murdoch and Lance Cade were no longer a tag team. It was revealed on WWE Unlimited, that Trevor Murdoch set his sights on Ric Flair and the WWE Intercontinental Championship.
After breaking up with Cade, he wrestled in singles competition on Heat, normally winning most of his matches while still making small appearances on Raw. He would also have a short feud with The Heart Throbs on Heat which involved him defeating both of them in singles action and gaining a spot in the 2006 Royal Rumble, though he did not win. He then moved on to a short feud with Goldust, but was unsuccessful in beating him. He would then feud with both Goldust and his tag partner Snitsky. This led to him helping former partner Cade win his matches and hinted at the two of them reforming their team.
Cade and Murdoch later reformed their tag team, with Cade having a new look with long jet black hair. On the September 4, 2006 edition of Raw, Murdoch and Cade lost a number one contender's triple threat match for the World Tag Team Titles at Unforgiven. The Highlanders won the match when they pinned Charlie Haas, who was teamed with Viscera. Murdoch and Cade then joined forces with Edge to oppose D-Generation X (Triple H and Shawn Michaels).
Cade and Murdoch began a feud in April 2007 with World Tag Team Champions The Hardys, leading to their title match at Backlash, which The Hardys won. Cade and Murdoch suddenly gained a great deal of respect for The Hardys and began to praise their abilities. The Hardys then began an alliance with Cade and Murdoch. Despite the alliance, Cade and Murdoch faced The Hardys in a rematch at Judgment Day, which The Hardys won. On the June 4 edition of Raw, Cade and Murdoch were given another shot at the World Tag Team Championship against The Hardys. Cade and Murdoch were finally successful, becoming two-time World Tag Team Champions. When Cade made the pin on Jeff Hardy, Hardy's foot was on the ropes but was pushed off by Murdoch. After the match, when Matt Hardy argued with Cade and Murdoch, they attacked Matt and Jeff with the tag belts, becoming heels once again. They successfully defended their titles against The Hardys at Vengeance: Night of Champions after Cade pinned Jeff and claimed they retained their belts "all by the rules". After that, Cade and Murdoch appeared on Raw and Heat in matches against Paul London and Brian Kendrick, The Highlanders, and Cryme Tyme. On July 23 on Raw, Cade and Murdoch teamed up with Umaga to face John Cena and Candice in a champions-only handicap tag team match. During the match, Cade and Murdoch trapped Candice in order to set her up for Umaga to attack, until Jeff Hardy came out and attacked Umaga with a steel chair. After Candice left scared, and Umaga was chased to the back by Jeff, Cade and Murdoch were left to square off against John Cena. Cena defeated them when he threw Cade out of the ring and gave Murdoch an FU. Murdoch, along with Cade lost the titles at a house show on September 5 to Paul London and Brian Kendrick, but beat them to take the titles back on the last day of the tour. Murdoch and Cade remained champions until the Raw XV Anniversary show, losing the World Tag Team Championships to the team of Hardcore Holly and Cody Rhodes.
Late in April 2008, Murdoch began to develop a country singing gimmick. On the May 12 edition of Raw, Cade turned on Murdoch following a "victory song," punching Murdoch in the face twice, ending the partnership. The two faced off on the June 2 edition of Raw, with Cade getting the victory.
As part of the 2008 WWE Supplemental Draft, Murdoch was drafted to the SmackDown brand, but was released from his WWE contract on July 3, 2008 before his debut.
Prior to the live broadcast of Raw on May 9, 2011, Murdoch wrestled as in a dark match, which he lost to Evan Bourne. He wrestled a dark match the following night prior to the SmackDown tapings, losing to Jey Uso.