Three-pointers by Wallace, Hamilton and Prince vaulted Detroit to a 79-57 lead with 10:03 remaining to give the Pistons a comfortable lead.
Billups connected on 7-of-14 from the floor for the Pistons, who also shot 8-of-18 from 3-point range.
Detroit's margin of victory over the Bulls is the largest by the Pistons in the playoff history between the two teams.
The previous high was a 22-point decision by Detroit, which beat Chicago 101-79 in game three of the 1988 Eastern semi-finals.
Detroit capped an 11-2 spurt with a 3-pointer by Wallace to take a 20-11 lead at the 5:21 mark in the first period. A basket by Ben Wallace and subsequent free throws with 49 seconds left helped the Bulls cut the lead to 29-23 at the end of the quarter.
Kirk Hinrich finished with 15 points for Chicago, but Ben Gordon, who was the second leading postseason scorer (25.5 points) for the Bulls entering this contest, added only seven points on 2-of-9 shooting from the floor as the Bulls shot just 33 percent.
Ben Wallace, the ex-Pistons center, had nine points and eight rebounds for Chicago, which was outrebounded, 46-38, by Detroit.
The second-seeded Cleveland Cavaliers will face the sixth-seeded New Jersey Nets in the other Eastern Conference playoffs semi-final series.
The Nets edged the third-seeded Toronto Raptors 98-97 to wrap up their first-round series in six games on Friday.
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