In 2005, Dominik made his first appearances in World Wrestling Entertainment (WWE) at the age of eight, as part of his father Rey Mysterio's ongoing feud with Eddie Guerrero, in which the two rivals fought for custody of him, and Guerrero stated that Mysterio was not his father. Mysterio defeated Guerrero at SummerSlam, ending the storyline. He once again appeared in 2010, this time during the feud between Rey Mysterio and the Straight Edge Society (CM Punk, Luke Gallows, and Serena).
On the March 19, 2019 episode of SmackDown Live, Dominick appeared on the show with his father, Rey Mysterio, who announced that he would be facing Samoa Joe at WrestleMania 35. He once again appeared on Raw from April to June, during the feud between Mysterio and Joe. In August, Mysterio teased his retirement due to multiple losses and amounting injuries. On the August 19 episode of Raw, Dominick appeared on the show, trying to persuade his father to not give up. On the September 30 episode of Raw, Dominick and Mysterio were brutally attacked by Brock Lesnar, resulting in a storyline injury for him. At Survivor Series, Dominick would attempt to help his father exact a measure of revenge by attempting to defeat Lesnar for the WWE Championship, but Mysterio failed.
In May 2020, he again assisted his father, this time in dealing with Seth Rollins and his teammates Murphy and Austin Theory, after his father suffered a severe kayfabe eye injury. At The Horror Show at Extreme Rules, Mysterio had his eye "removed" in an "Eye for an Eye" match, where the winner could only be declared upon removing an opponent's eyeball from its socket. Dominick thereafter came for revenge, but coming at Rollins proved unsuccessful, with Dominick having to be saved by his father's ally, Aleister Black. On the August 3 episode of Raw, Dominick issued a challenge to Rollins, which he accepted for SummerSlam, in what would be Dominick's in-ring debut. The following week, after making their SummerSlam match official, Rollins and Murphy would brutalize a helpless Dominik with over thirty kendo stick shots. At SummerSlam, Dominik made his in ring debut, where he was defeated by Rollins in a street fight. At Payback, Dominik teamed with his father to defeat Rollins and Murphy for his first victory in WWE. The next night on Raw, Dominik replaced his injured father in a match with Rollins, set up to determine entries into another match that was held later that night to decide the next challenger for the WWE Championship. Rollins avoided a frog splash, and went on to defeat Dominik, as a frustrated Rey looked on backstage. The next week, he defeated Murphy with the help of his family in a street fight. The following week on Raw, he once again wrestled Rollins, this time in a steel cage match, where he was defeated.
As part of the 2020 draft in October, Mysterio was drafted to the SmackDown brand. The Mysterio family's feud with Rollins would end on the November 13 episode of SmackDown after Rey defeated Rollins in a No Holds Barred match after assistance from Murphy, who turned on Rollins. On the Survivor Series kickoff, Mysterio took part in a dual brand battle royal where he was the last person eliminated by The Miz. In January 2021, Dominik and Rey would begin a feud with King Corbin. On the January 22, episode of SmackDown, Dominik was defeated by Corbin and would lose a rematch the following week. At the Royal Rumble, Dominik took part in his first Royal Rumble match, where he eliminated Corbin before being eliminated by Bobby Lashley. Five days later on SmackDown, he defeated Corbin in a singles match despite being attacked from behind by Corbin before the match started. On the February 12 episode, the Mysterios were defeated by Corbin and Sami Zayn in an Elimination Chamber qualifying match. On the WrestleMania edition of SmackDown, Dominik and Rey Mysterio would face Dolph Ziggler and Robert Roode, Chad Gable and Otis, and The Street Profits in a fatal four-way tag team match for the SmackDown Tag Team Championships, but were unsuccessful as Ziggler and Roode retained their titles. At WrestleMania Backlash, they won the tag team championships from Ziggler and Roode, marking Dominik's first championship in WWE, and making him and Rey the first father and son tag team champions in WWE history. At Money in the Bank, The Mysterios dropped the titles to The Usos, ending their reign at 63 days. A rematch for the titles was set for SummerSlam, but the Mysterios failed to regain the titles. On the September 24 episode of SmackDown, Dominik teased a possible heel turn after blaming his father Rey Mysterio for his losses against Sami Zayn from the past two weeks.
As part of the 2021 Draft, both Rey and Dominik were drafted to the Raw brand. At the Royal Rumble on January 29, Dominik entered the Royal Rumble match at number fourteen, but was quickly eliminated by Happy Corbin. On the February 21, 2022 edition of Raw, The Miz challenged The Mysterios to a tag team match at WrestleMania 38, with Logan Paul as his partner, which they accepted. At the event, the Mysterios lost to Paul and The Miz. On the following episode of Raw, Dominik lost to The Miz in a singles match after which he and his father were attacked by Veer Mahaan. Dominik would face Mahaan in a match alone, only to be easily defeated and taken out on a stretcher.
Following this, The Mysterios began feuding with The Judgment Day (Finn Bálor, Damian Priest and Rhea Ripley) over their attempts to recruit Dominik into the group and betray his father. At SummerSlam on July 30, The Mysterios defeated Bálor and Priest following interference from Edge, The Judgment Day’s former leader. After losing an Undisputed WWE Tag Team Championship match on the following episode Raw, The Judgment Day attacked the Mysterios before Edge came out to save them, but accidentally speared Dominik in the process. The next week, Dominik confronted Edge backstage, pushing him in the process. His father stopped him before he did anything else, and Dominik walked away. Later that night, Ripley walked out on the stage in the middle of his father's match, and laid down a bloodied and bruised Dominik, distracting Rey long enough for Bálor to get the victory.
Dominik sat out the match between the Judgment Day and the team of Edge and Rey at Clash at the Castle, but after the match, he assaulted both Edge and his father, turning heel in the process for the first time in his WWE career. On the following episode of Raw, Dominik officially joined The Judgment Day, helping the group attack Edge and Rey. The following week, Dominik challenged Edge to his first singles match as a heel, but was unsuccessful after Finn Bálor attacked Edge with a steel chair, making Edge the victor by disqualification. On the October 17 episode of Raw, Dominik scored the biggest singles win of his career at that point by pinning AJ Styles after interference from Rhea Ripley. At Crown Jewel on November 5, Dominik, Bálor, and Priest defeated The O.C. (AJ Styles, Luke Gallows and Karl Anderson) in a six-man tag team match after interference from Ripley. On the November 28 episode of Raw, The Judgment Day defeated The O.C in an eight-person mixed tag team match to end their feud.
On Thanksgiving, Dominik was filmed inviting Ripley to the Mysterio family home. After Rey refused to let them into the house, Dominik and Ripley attacked Rey. On Christmas Eve, Dominik and Ripley visited Dominik's grandparents' home. A confrontation ensued between Dominik, Ripley, Rey and Angie (Rey's wife and Dominik's mother) outside of the house, with Dominik shoving Rey and Angie slapping Ripley. The police arrived shortly after and arrested Dominik. After being released from police custody, Dominik, Bálor and Priest won a Raw Tag Team Championship opportunity against The Usos by winning a tag team turmoil match on the January 9, 2023 episode of Raw. At Raw is XXX on January 23, The Usos successfully defended the championships against Dominik and Priest despite Jimmy Uso's injury, with Sami Zayn taking Jimmy's place. At the Royal Rumble on January 28, Dominik, perhaps with the entire The Judgment Day, presumably took out his father who was scheduled to enter at number seventeen. Dominik then entered at number eighteen, but was eliminated by the eventual winner Cody Rhodes.
On the March 10 episode of SmackDown, Dominik and The Judgment Day interrupted Rey as he was addressing being the first inductee into the WWE Hall of Fame class of 2023. After The Judgment Day defeated Legado del Fantasma (who had recently turned face and sided with Rey) in a six-man tag team match, Dominik taunted and goaded Rey into hitting him, saying that Rey was a "deadbeat dad." On the following episode of Raw, Dominik interrupted Rey again and challenged him to a match at WrestleMania 39. Rey declined, saying he would never fight his own son. On the penultimate episode of SmackDown before WrestleMania 39, Dominik continued to demand Rey a match at WrestleMania. When Rey left the ring, Dominik berated his mother, Angie, who was at ringside with his younger sister, Aalyah, for being supportive of Rey and called her a "deadbeat mom". Angie then pulled the mic away and Dominik snatched it back, telling Angie to "shut up". Rey walked back to ringside, punched Dominik, and accepted his challenge. During the 2023 Hall of Fame ceremony, Dominik, Ripley and Priest all remained seated while the rest of the roster stood up to applaud Rey during his entrance for his Hall of Fame induction. The trio then left their seats and walked backstage as Rey was about to start his induction speech. At WrestleMania Night One, Dominik lost to Rey after interference from Legado del Fantasma and Bad Bunny. On the Raw after WrestleMania 39, Dominik confronted Bad Bunny for his involvement in Dominik's match against Rey. Bad Bunny would hit Dominik, which led to Priest chokeslamming Bad Bunny through the announcer's table. On the June 5 episode of Raw, Dominik crashed Miz TV, calling Cody Rhodes a "bad father" and "a deadbeat dad." The following week, Cody Rhodes challenged Dominik to a match at Money in the Bank, which Ripley accepted on his behalf. At the event, Dominik lost to Rhodes despite interference from Ripley.
On July 18, Dominik Mysterio claimed his first singles title when he defeated Wes Lee on NXT for the NXT North American Championship. On the following episode of SmackDown, Dominik defeated Butch of The Brawling Brutes to retain the title. On the following episode of Raw, Dominik successfully defended the title against Sami Zayn. At NXT The Great American Bash on July 30, Dominik successfully defended the title against Wes Lee and Mustafa Ali in a triple threat match. On the August 8 episode of NXT, Dominik retained the title against Dragon Lee. At Payback on September 2, Dominik helped Bálor and Priest capture the Undisputed WWE Tag Team Championships from Kevin Owens and Sami Zayn and helped Ripley retain the Women's World Championship against Raquel Rodriguez. On the September 25 episode of Raw, Dominik once again defeated Dragon Lee to retain his title. On September 30 at NXT No Mercy, Mysterio lost the North American Championship to Trick Williams, ending his reign at 74 days. Three nights later on NXT, Dominik defeated Williams in a rematch to win the NXT North American Championship for the second time. On the following episode of NXT, Dominik failed to win the NXT Championship from Ilja Dragunov after interference from Williams. On night two of NXT Halloween Havoc on October 31, Dominik successfully defended his title against Nathan Frazer. At Survivor Series WarGames on November 25, Dominik participated in his first WarGames match alongside The Judgment Day (which now included JD McDonagh) and Drew McIntyre against Cody Rhodes, Jey Uso, Seth "Freakin" Rollins, Sami Zayn and a returning Randy Orton in a losing effort. At NXT Deadline on December 9, Dominik lost the NXT North American Championship to Dragon Lee, ending his second reign at 67 days.
On January 27, 2024, Dominik entered the men's Royal Rumble at number nine, eliminating Carmelo Hayes and Bron Breakker before being eliminated by CM Punk. On night one of WrestleMania XL on April 6, Dominik teamed up with Legado del Fantasma's Santos Escobar against his father, Rey, and Andrade in a losing effort after interference from Lane Johnson and Jason Kelce. On the April 15 episode of Raw, Dominik suffered an elbow injury during a match with Andrade. During this time, he began a storyline with Liv Morgan, having accidentally helped her defeat Becky Lynch to win the Women's World Championship at King and Queen of the Ring on May 25. On the following episode of Raw, in a bid to help Lynch win back the title, Dominik again interfered in Lynch and Morgan's match. Morgan however retained, and kissed Dominik after. Over the next several weeks on Raw, as part of her plan to take everything from Rhea Ripley, Morgan continuously flirted with Dominik in an attempt to win him over. On the July 8 episode, they teamed together to face Rey Mysterio and Zelina Vega. Dominik won the match by pinning his father for the first time, and almost kissed Morgan after, but they were interrupted by a returning Ripley. Dominik was able to win back Ripley's trust on the July 22 episode of Raw by publicly telling Morgan he hated her and making her cry, but at SummerSlam only two weeks later, he helped Morgan retain her title and ultimately betrayed Ripley. Dominik and Morgan then went on to face Ripley and Damian Priest in a losing effort at Bash in Berlin.