A night after Detroit's first defeat of the season, Billups made five 3-pointers in the second half in a victory that left Boston as the NBA's lone unbeaten team.
"We needed to get that taste out of our mouths from last night; especially against a team that's been going good." said Billups, who was 5-for-7 from behind the arc in the third quarter.
McDyess, who attempted just four field goals in Thursday's loss, made all seven tries from the floor and scored all 14 points in the first half as the Pistons took command early.
"I knew in warmups I felt pretty good and just kind of transported it to the game," McDyess said. "I made the first couple and they just kept coming.
"It was important to play an all-around game tonight to give us some confidence going out on the road."
The Pistons begin a five-game West Coast road trip Sunday at Seattle. They don't return home until Nov. 21.
Detroit made 15 of its 20 first-quarter field-goal attempts, including three straight during a 9-0 run that gave it the lead for good. The Pistons scored the first 10 points of the second quarter and led by as many as 20 before taking a 59-42 lead to intermission.
"We played pretty focused from the beginning," Detroit coach Flip Saunders said. "We played with good energy."
The Pistons outrebounded Los Angeles 53-33.
"They controlled the glass and the tempo of the game and shot the ball really well," Clippers coach Mike Dunleavy said. "We didn't have guys make shots."
The Clippers, who won their first four games, never got closer than 13 in the second half.
Center Chris Kaman, who entered the game leading the league in rebounding, had 25 points but only seven rebounds -- almost nine below his 16.5 average -- for Los Angeles. Corey Maggette added 19 points.
"We weren't ready to play defensively tonight," Kaman said. "It just wasn't our night."
Sam Cassell, who scored 35 points in Wednesday's victory at Indiana, had only four Friday on 1-for-5 shooting.
The Clippers were without guard Cuttino Mobley, who missed the game after a hip injury against the Pacers. He's expected to miss at least a week.
Maggette (bruised tailbone), F Ruben Patterson (finger) and G Brevin Knight (back) all played for Los Angeles after being listed as game-time decisions. ... The Clippers were seeking their first 5-0 start since the 1985-86 season. ... Detroit sold out its 187th consecutive game.