The Bucks had won three consecutive games, averaging 106 points during the streak. The Pistons, starting 6-foot-9 Amir Johnson in place of Hamilton, a slim 6-7 guard, held Milwaukee to 30 percent shooting.
"Everything got started because defensively we were very good," Detroit coach Michael Curry said.
Johnson had eight points, 11 rebounds and four blocked shots, giving the Pistons a different defensive look from their usual lineup that consists of 6-11 Rasheed Wallace as their only big starter.
The Pistons acknowledged after the game that they are better defensively with Johnson on the floor, and better offensively when Hamilton and Iverson are on the court together with guard Rodney Stuckey.
"When we have the bigger lineup, obviously we're better defensively," Prince said. "It's kind of pick and choose. "Sometimes you are going to need the offensive side, but more importantly you're going to need the defensive side."
The game was tight until Detroit went on a 27-5 run midway through the third quarter. Milwaukee missed 14 of 17 shots during one stretch of the period, trailed 73-55 after three quarters and never got close again.
"We've been good [defensively] in stretches, especially with two bigs on the floor," Curry said. "With the small lineup that we usually start, we give up that inside presence. Not having that other big, teams attack even more to the inside. When they attacked today, if they did get by Amir or Rasheed, the other one was there to protect the basket. They also didn't attack the paint nearly as hard."
Andrew Bogut had 17 points and 10 rebounds for Milwaukee, which mainly rested its starters for the final 15 minutes after the game was decided. Michael Redd, the Bucks' leading scorer, had four points and missed nine of 11 shots, including his last five.
"Because I'm putting the other guys in doesn't mean I'm giving up on the game," Milwaukee coach Scott Skiles said. "I still intend to win the game. It can be very confusing on certain nights of why certain guys just don't have it, but it does happen in the NBA."
Hamilton missed the game with a groin injury that he aggravated in Friday night's victory over Oklahoma City. He is listed as day to day, and Curry recognizes the need to get him back in the lineup.
"We all understand that we have two shooting guards and both of them are very, very good," Curry said. "We need to give them fair time on the court so they can be productive. Because of that we lose some time with our bigs."
The Pistons beat Milwaukee for the 10th time in 13 meetings since the 2005-06 season.
Wallace had 16 points and 12 rebounds, and Stuckey added 16 points for Detroit, which has won three straight and six of eight.
"It's a bit discouraging to lose at home, but we've had one bad game out of the last six or seven home games," Bogut said. "That's no excuse."
The Pistons missed their first five shots of the second half and Luke Ridnour's jumper gave Milwaukee its last lead, 48-46, with 10:35 left in the quarter.
Stuckey then tipped in his own missed layup to tie the score at 48, starting a 27-5 run in which Detroit made 11 of 15 shots to take a 73-53 lead on Prince's free throw with 19 seconds left in the period.
Prince had nine points, four rebounds, two assists and a steal in the third.
Milwaukee was so out of sync that Skiles went with a lineup of Malik Allen, Joe Alexander, Tyronn Lue, Dan Gadzuric and Ridnour with 3:40 left in the third quarter, leaving most of the starters on the bench the rest of the way.
Milwaukee G Damon Jones joined the team. Jones was obtained in an offseason trade, but he hasn't played for the Bucks by mutual agreement as they worked with his agent in an attempt to work out another trade. When a deal never materialized, Jones reported to the team Saturday night and was inactive