Smith, coming off a 31-point performance Sunday against Portland, also grabbed seven rebounds for Detroit, which snapped a 10-game road losing streak against the Pacers.
Greg Monroe added 13 points and 12 rebounds as the Pistons won for just the third time in seven games overall.
Brandon Jennings helped out with 18 points and eight assists.
Lance Stephenson fired in a career-high 23 points and provided seven rebounds with six assists for the Pacers, who had begun the season with an 11-0 mark on their home court.
Paul George chipped in 17 points with nine rebounds and Luis Scola came off the bench to add 18 points.