Josh Smith had 22 points and 11 rebounds as the Hawks (5-0) remained the only unbeaten team in the Eastern Conference.
Ben Gordon had 22 points but it wasn't enough for Detroit.
The Pistons are 0-5 for the first time since the 1980-81 season, when they started 0-7. They won their fifth game after starting 0-4 in 1999-2000.
Tayshaun Prince, who had 17 points, hit a 3-pointer to give Detroit an 81-76 lead. The Hawks then took over with the closing run over the final 6:13.
Horford had 18 points, Joe Johnson added 14 and eight assists, Zaza Pachulia had 12 points and Marvin Williams added 11.
Charlie Villanueva had 14 points for Detroit.
The Pistons used their 17-3 advantage in offensive rebounds to take a 16-6 lead in second-chance points. The Hawks averaged 44 rebounds in their first four wins, but they were outrebounded 38-35 by the Pistons.
The Hawks led 70-66 entering the final period. Gordon opened the final period with consecutive baskets to start a 10-2 run that gave the Pistons a 76-72 lead.
The Hawks were without top sub Jamal Crawford, who suffered a right turf toe injury in Tuesday night's win at Cleveland. Crawford, chosen as the NBA's Sixth Man of the Year last season, is averaging 15.8 points per game. It's not known how long he will be sidelined.
The Hawks already were without another top backup, guard Maurice Evans, who missed his fourth straight game with a right knee injury.
Hawks rookie Jordan Crawford, who played only two minutes over the first four games, moved into a more prominent role and scored his first career points with a jumper late in the first quarter. It was his only basket of the game.
The Pistons took advantage of Gordon's matchup with Mike Bibby. Gordon opened the game with a reverse layup and continued to attack Bibby, scoring 11 of the Pistons' first 16 points.
Gordon had 14 points in the first half to give Detroit a 48-44 lead.
Notes: Hawks F Marvin Williams left the game with 6:34 remaining after landing hard in a battle with Greg Monroe for a loose ball. ... Pistons G Richard Hamilton (sore right foot) missed his second straight game. F Tracy McGrady played after he was listed as questionable with a sore left knee. ... The Hawks shot 60 percent from the field in the first half and still trailed 48-44. They shot 53.7 percent for the game.