The Bulls routed the Cavaliers with most of their top players, including Derrick Rose, being rested ahead of the post-season, where they meet the eighth-seeded Philadelphia 76ers, who closed out their campaign with a 108-86 loss to the Detroit Pistons.
"Last year we had to rely heavily on (Rose's) scoring to have a good chance (in the playoffs)," Bulls coach Tom Thibodeau told reporters. "This year Derrick does not have to score like that. We have a number of guys who can score.
"We have a lot more scoring."
Going into the NBA's regular season finale there was plenty on the line in the final 13 games with only two of the eight matchups set and home court advantage decided.
The 76ers loss combined with the New York Knicks 104-84 win over the Charlotte Bobcats setup an intriguing matchup between the seventh-seeded New Yorkers and East second seed the Miami Heat.
The Knicks also rested their key starters but easily dismissed the Bobcats, who suffered their 23rd consecutive loss to finish with a 7-59 record and the worst winning percentage (.106) by a NBA team.
Miami's big three, LeBron James, Dwyane Wade and Chris Bosh were also rested and the Heat paid the price with their worst defeat of the season, a 104-70 loss by the Washington Wizards.
Other first round matchups in the East will see the Indiana Pacers facing off against the Orlando Magic and the Boston Celtics taking on the Atlanta Hawks.
The Bulls-76ers and Heat-Knicks begin the NBA's postseason on Saturday, while last season's champions the seventh seeded Dallas Mavericks face the second seed Oklahoma Thunder in a rematch of last year's Western conference finals.
The West's top seed, the San Antonio Spurs, open against eighth seed Utah Jazz while Kobe Bryant, who sat out the Lakers' last game forfeiting any chance of claiming the scoring crown, will lead Los Angeles against the Denver Nuggets.
The Memphis Grizzlies clinched the fourth seed and home court advantage for the first time in a playoff series when they closed out the regular season with an 88-76 win over the Magic to set up a first round showdown with the Los Angeles Clippers.
"I have to say, 'mission accomplished'," Grizzlies guard Tony Allen said. "Obviously there's plenty more work to be done but this is what we set out to do. We've got to stay focused."