He made his main-roster debut on the April 16, 2007 edition of WWE Raw in Milan, Italy, as a planted fan named Santino Marella. Marella's debut, in which he took the WWE Intercontinental Championship from Umaga in a No Holds Barred match after interference from Bobby Lashley, resulted in both that night and Santino himself being dubbed "The Milan Miracle". The surname Marella was chosen for the character in honor of WWE Hall of Famer Gorilla Monsoon—real name Robert Marella—and was given to Carelli shortly before the trip to Italy. The next day WWE.com posted a profile on Marella with a fictional background saying he was an Italian national who moved to Canada as a child and returned to his native country a few times each year to visit family. It further stated that he moved to the U.S. to begin training with the goal of breaking into professional wrestling, and ultimately WWE.
Shortly after gaining the Intercontinental Championship, Marella started a scripted rivalry with Chris Masters, narrowly retaining the title over him in his first defenses. He held the Intercontinental Championship for three months before dropping it back to Umaga on July 2, after having just defeated him at the June 24 Vengeance: Night of Champions pay-per-view by disqualification when Umaga stopped listening to referee's instructions and continued punching Marella.After losing the title Marella's character became increasingly villainous; he was depicted as possessive and jealous of his girlfriend WWE Diva Maria. Over several weeks they appeared together in a series of segments on Raw, including two mini "game shows" hosted by General Manager William Regal which resulted in retired wrestler Ron Simmons winning a date with Maria, much to Santino's dismay. At the same time Marella, began a campaign of bashing the WWE Films production The Condemned as its DVD release neared. He was eventually confronted by the film's star, Steve Austin, who argued the film's merits before delivering a Stone Cold Stunner to Marella and soaking both him and Maria down with a hose from a Budweiser truck. During the Austin program, Marella repeatedly mocked Austin and mangled the English language and his catchphrases in promos, giving his character a new humorous bent.After a short program with Jerry Lawler, he was placed into a tag team with Carlito. At the same time, Maria was chosen to be pose for Playboy magazine, which was used as part of their storyline. When he was unable to get her to turn the offer down, he attempted to sabotage the cover unveiling, finally pushing Maria to break up with him. At WrestleMania XXIV, Maria was involved in a "Playboy BunnyMania Lumberjack match", during which Santino interfered only to get clotheslined by celebrity Master of Ceremonies Snoop Dogg after the match. Marella's feud with Maria came to an end after she defeated him on the episode of Raw the day after WrestleMania. Marella and Carlito began a feud with Hardcore Holly and Cody Rhodes over the World Tag Team Championship. During a title match between the two teams, Roddy Piper distracted Marella, who was then pinned and so lost the match for his team. Due to the distraction, Marella started a rivalry with Piper, including a confrontation on Jimmy Kimmel Live!.
On the July 14, 2008 episode of Raw, Marella was defeated by WWE Diva Beth Phoenix in a match. Marella issued an open challenge to the entire Raw roster. The angle continued the following week after Marella lost to the returning D'Lo Brown. Marella and Phoenix shared a kiss, both expressing considerable confusion afterwards. In later weeks, they became an on-screen power couple, later called "Glamarella", a portmanteau of "Glamazon" (Phoenix's nickname) and "Marella". At SummerSlam, Marella won the Intercontinental Championship for a second time, when he teamed with Phoenix against champion Kofi Kingston and WWE Women's Champion Mickie James. Phoenix pinned James after hitting her Glam Slam, thus winning both titles for her team per the pre-match stipulation.
During his second reign, Marella started a quest to become the "greatest Intercontinental champion of all the times" by beating The Honky Tonk Man's record reign of 64 weeks, constantly bringing out a status report called the "Honk-A-Meter". At Cyber Sunday, Marella defended the Intercontinental title against the Honky Tonk Man (who won the majority of fan's votes, beating fellow former champions Roddy Piper and Goldust), losing by disqualification. On the November 10 episode of Raw, Marella lost the title to William Regal and thus failed to reign as champion for more than 64 weeks.
At the beginning of 2009, Marella entered the Royal Rumble drawing number 28. He was instantly eliminated by Kane in 1.9 seconds, thus breaking The Warlord's two second record for shortest Royal Rumble appearance at the 1989 Royal Rumble.
Following the announcement of a 25-Diva battle royal at WrestleMania XXV to crown the first-ever "Miss WrestleMania", Marella began a face turn and was placed in an angle in which he expressed his desire to compete in the match. The storyline called for Marella to challenge Mickie James in a match where he had one arm tied behind his back, and if he won, he would gain entry into the match. He lost, however, and, as a result, the following week, in a bid to prove he was eligible to compete, he revealed he was wearing a mankini, but was subsequently attacked by most of the Divas on the roster. Nevertheless, at WrestleMania XXV, Marella won the 25 Diva battle royal, competing in drag under the disguise of "Santino Marella's twin sister, Santina", and last eliminating Phoenix and Melina. On the May 18 episode of Raw Santina lost the "Miss Wrestlemania" title to Vickie Guerrero. Marella won it back at Extreme Rules when he defeated Vickie Guerrero and Chavo Guerrero in a Handicap Hog Pen match. On the June 22, 2009 episode of Raw, the new (kayfabe) owner of Raw, Donald Trump fired Santina, thus ending the storyline. As of late, he has been seen in backstage segments with the nights special guest host. He has also been involved in the feud between Chavo Guerrero.