Malenko signed with the World Wrestling Federation (WWF) and debuted on January 31, 2000 edition of Raw Is War. Malenko first appeared in the crowd with the infamous Radicalz – himself, Chris Benoit, Perry Saturn, and Eddie Guerrero. While not having as much success in the WWF, Malenko was a force in the promotion's light heavyweight division. Along with Benoit, Saturn, and Guerrero, he had some measure of success as part of The Radicalz. On the March 13 edition of Raw Is War, Malenko defeated Essa Rios for his first WWF Light Heavyweight Championship. In April 2000, he feuded with Scotty 2 Hotty who was the new challenger for his Light Heavyweight title. He dropped the title to Scotty on April 17 edition of Raw Is War before he won his second WWF Light Heavyweight Championship from Scotty on April 27 episode of SmackDown!. At Backlash 2000, Malenko successfully defended the title against Scotty, thus ending the feud between the two.
Later that year, with Benoit having drifted away from the group, Malenko engaged in a feud with Guerrero and Saturn which stemmed from Guerrero's on-screen relationship with Chyna and a number of losses suffered when working as a tag team with Saturn. The feud led to a triple threat match at Judgment Day 2000 where Guerrero retained the WWF European Championship against both Malenko and Saturn. After a brief absence from TV, Malenko returned to reform The Radicalz with Benoit, Guerrero, and Perry Saturn. Around this time, Malenko briefly became known as "Double Ho Seven". The gimmick was born out of a match with The Godfather, who offered one of his female escorts to Malenko instead of wrestling him. Malenko gladly accepted his opponent's offer. As Double Ho Seven, Malenko competed for the affections of Lita and feuded with her tag team the Hardy Boyz. He even offered Lita a title match for his Light Heavyweight Championship, but under the condition that if she lost she would be obliged to go on a date with him. Lita accepted and almost caught Malenko by a few nearfalls throughout the match, but in the end lost the match by submitting to his signature Cloverleaf.
Malenko's feud with Hardy Boyz and Lita continued in early 2001, culminating with Lita pinning him (with some assistance from Matt Hardy) in a match on February 19, 2001 edition of Raw Is War. He also briefly feuded with Jacqueline and Ivory, who were disgusted by his lecherous ways. A title feud with Crash Holly would begin after Crash interfered in a two-on-one intergender handicap match between Malenko, and both Jacqueline and Ivory, costing him the match. After holding the Light Heavyweight Championship for nearly twelve months, Malenko lost the title to Crash on March 18 episode of Sunday Night HEAT. After both Benoit and Guerrero drifted away from the Radicalz, Malenko teamed with Saturn for a few weeks before quietly disappearing off television as the Invasion storyline began in summer 2001.
Malenko appeared in the ring along with other legendary wrestlers during a segment of the WWE Homecoming edition of Raw on October 3, 2005. His friend Eddie Guerrero died on November 13, 2005 and Malenko made a special appearance on the November 14 edition of Raw alongside Chris Benoit, speaking about Eddie's death and talking about the memories they had shared together. The following Friday on SmackDown!, Malenko once again appeared after a match between Chris Benoit and Triple H, and the three embraced. After the 2006 Royal Rumble, he was seen congratulating Rey Mysterio on his Rumble victory. At Vengeance 2007, he appeared in a backstage segment watching Chavo Guerrero. On the Chris Benoit memorial episode of Monday Night Raw, he talked about the life of Chris Benoit. He was very sad since two of his close friends, Eddie and Benoit, both died, but said he was happy that they were together again. Dean then made an appearance on the March 31, 2008 edition of Raw to join The Four Horsemen and other WWE superstars in a farewell tribute to Ric Flair. He made an appearance on the June 28, 2010 episode of Raw congratulating Ricky Steamboat on his DVD release. He and all the others in the ring were attacked by the Nexus.