Arn Anderson and Tully Blanchard joined Vince McMahon's World Wrestling Federation. Upon being named the Brain Busters, the team took Bobby "The Brain" Heenan as their manager and quickly began rising through the tag team ranks, eventually coming to challenge Demolition for the WWF Tag Team Championship. On July 18, 1989, the Brain Busters won the titles, ending Demolition's historic reign of 478 days; the match would air on the July 29 edition of Saturday Night's Main Event. Although they would lose the titles back to Demolition just over three months later, the Brain Busters continued to be a force in the WWF's tag team division.
Anderson became a road agent for WWF, renamed World Wrestling Entertainment (WWE) in May 2002. He occasionally appears on WWE television trying to, with the help of other WWE management, pull apart backstage brawls.
He made an appearance on Raw in 2002 delivering a video to Triple H before he was supposed to renew his wedding vows to then-heel, Stephanie McMahon. Anderson was also assaulted on Raw by the heel gimmick of The Undertaker leading up the Undertaker vs. then-babyface, Ric Flair match at WrestleMania X8. During that bout, Anderson made a brief in-ring appearance, delivering his signature spinebuster to The Undertaker. He would later turn heel once again by helping the heel gimmick of Ric Flair in his feud with Stone Cold Steve Austin, leading to Austin literally urinating on him. Several months later he became a face once again and attempted to help a then-babyface Flair gain (kayfabe) sole ownership of WWE during a match with the heel gimmick of Vince McMahon, but backed down from a confrontation with Brock Lesnar, who entered the ring to assist McMahon.
Anderson made a special appearance at the October 2006 Raw Family Reunion special, in which he was in Ric Flair's corner for his match against Mitch of the Spirit Squad. Anderson was in the corner of Flair, Sgt. Slaughter, Dusty Rhodes, and Ron Simmons at Survivor Series 2006, where the four faced the Spirit Squad, but was ejected from the arena during the match.
On the March 31, 2008 Raw, Anderson came out to say his final goodbye to Ric Flair and thank him for his career. In October of that year, at the No Mercy event, he was backstage congratulating Triple H for retaining the WWE Championship in a match with Jeff Jeff Hardy.
In 2012, he was inducted into the Hall of Fame as part of the Four Horsemen.