Acquired in the offseason from the Super Bowl champion New England Patriots for a 2003 first-round draft pick, Bledsoe was brought to the Bills to be the franchise quarterback the club has been missing since Hall of Famer Jim Kelly retired following the 1996 season.
Trying to shake off some of the rust after he was supplanted as the starter by Tom Brady last season, Bledsoe looked good for his new team, going nine of 11 for 136 yards and two touchdowns with an interception.
Bledsoe had a 31-yard touchdown pass to Eric Moulds on the game's opening drive and found Peerless Price from 12 yards early in the second quarter before departing.
"I'll be honest, I had a little pregame jitters going on," Bledsoe said. "I was a little nervous, a little anxious. I was real excited to get out there and get a game under my belt."
A bust since being selected third overall in the 1999 draft, Smith played the second half and helped the Bengals erase a 17-14 deficit.
Smith completed 10 of 17 passes for 72 yards, including a six-yard touchdown to Sean Brewer late in the third quarter that gave the Bengals a 21-17 lead.
Kitna started and went seven of 10 for 51 yards. Frerotte was six of 10 for 67 yards with a touchdown and an interception.
Rudi Johnson, a 2001 fourth-round pick, led the Bengals' ground game with 14 carries for 100 yards.
Cincinnati's Peter Warrick, the fourth overall pick the year after Smith, had six receptions for 47 yards and a touchdown.