Callum Robinson could have opened the scoring inside the opening 15 minutes when he created some space in the box before unleashing a low drive, but Gary Woods was able to make the stop.
The teenager did manage to break the deadlock a few minutes later when Chris Humphrey crossed the ball in for Robinson to tap in his first senior goal from close range.
Joe Garner could have doubled Preston's lead shortly before half time, but his header from close range could not get the better of Woods.
Preston continued to look the stronger of the two sides early in the second half, and managed to increase their advantage when Tom Clark crossed the ball across the face of goal from Paul Huntington to smash in from close range.
David Buchanan attempted to end any chances of an Orient comeback with a long-range effort inside the final five minutes, but the shot was always rising.
The result means that Orient make a losing start under new manager Mauro Milanese, leaving them 19th in the table, while Preston sit second, just two points behind leaders Bristol City with a game in hand.