Matt Barnes had 18 points and nine rebounds for the Magic and Jameer Nelson also scored 18, with eight assists.
Orlando had lost 20 of 25 regular season games to the Pistons, including one earlier in the week.
The closest Detroit came on Friday night was 96-90 after a shot by Villanueva with about three minutes to play.
Rodney Stuckey scored 20 points and Ben Gordon finished with 19 for the Pistons.
Three nights after fouling out with eight points in 17 minutes, Howard was nearly perfect. He made 7 of 8 field goals and 8 of 9 free throws and didn't even commit a foul until after halftime.
The Magic, who were already without Vince Carter (sprained left ankle) and Rashard Lewis (10-game suspension) lost starting power forward Ryan Anderson to a sprained right ankle in the third quarter.
Detroit was without starters Rip Hamilton (right ankle sprain) and Tayshaun Prince (lower back strain).
The Pistons were staying at a downtown hotel less than mile from where a gunman opened fire and killed one person and wounded five others late Friday morning, causing a shutdown of city streets during a search for the assailant. They had to detour returning to the team hotel after the morning practice.
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