In the 2006 NBA Playoffs, the Wizards matched up with LeBron James and the Cleveland Cavaliers in a 4-5 first-round matchup, in what would turn out to be the first of (as of 2008) three consecutive postseason matchups, as well as James' first-ever playoff appearance. The series was considered to be one of the most evenly matched of all first-round series that year. After suffering a loss in Game 1, Washington came back to win Game 2 and steal home-court advantage heading back to Verizon Center for Game 3. However, Cleveland stole home-court advantage right back. Washington came back to tie the series at two apiece with a win in Game 4, but suffered two consecutive one-point overtime losses and thus were eliminated 4 games to 2.

The Wizards and Cavaliers met again in the 2007 NBA Playoffs, this time as a 2-7 matchup. The injury-riddled Wizards (they were missing Gilbert Arenas and Caron Butler) were swept 4-0 by Cleveland. Antawn Jamison averaged a team-high 32 points per game in the series.

In April of 2008, Arenas made comments saying Cleveland was only a .500 team since a midseason blockbuster trade. After the conclusion of the 2007-08 regular season, the Wizards and Cavaliers were pitted against each other yet again in a 4-5 first-round matchup. Following a regular-season win on March 13th, guard DeShawn Stevenson made comments saying LeBron James was "overrated." James responded to the comment by saying that he wouldn't return the insult, as that would be "almost like Jay-Z [responding to a negative comment] made by Soulja Boy."[11] Soulja Boy made an appearance at Game 3 of the series (played in Washington) in support of the Wizards; his music was played over the PA system[12]. Jay-Z, a close friend of James, got involved in the rivalry as well, making a song that trashed Stevenson. The day after Game 3, James reserved a private room at a D.C. area nightclub called "Love" for himself and his teammates. Jay-Z's new song was played while Cavs guard Damon Jones made negative gestures about the Wizards. Unbeknownst to the Cavaliers, Wizards star Caron Butler and his wife were also present, and they stormed out of the nightclub. According to the ABC broadcast of Game 4, Butler and the Wizards have sworn never to visit that particular club again, despite often frequenting it in the past. After suffering a late-game loss in Game 4 at the hands of a Delonte West three-pointer, Washington won a nail-biting Game 5 in Cleveland to bring the series back to Washington for Game 6 of the series. Prior to Game 6, Darius Songaila, a reserve forward, was suspended for hitting LeBron James in the face in the first quarter of Game 5, and without Songaila, the Wizards suffered a season-ending defeat to Cleveland, and lost the series 4-2.

Dating back to the start of the 2005-06 season, the Wizards and Cavaliers have played each other a combined 30 times (including preseason), far more than they have played any other team in the league.