The visitors made the perfect start as Jermaine Beckford’s cool finish put them ahead after just six minutes at the Proact Stadium.
Chesterfield responded well and controlled much of the match but they struggled to create many clear-cut chances against a well-organised Preston defence.
Substitute Ollie Banks went closest for the Spireites when he failed to convert at the back post from Sam Clucas’s cross in the 82nd minute.
The second leg at Deepdale takes place on Sunday with the winner facing either Swindon or Sheffield United in the final.
Preston will be the favourites to go to Wembley after putting the disappointment of missing out on automatic promotion behind them with a gritty performance at the Proact Stadium.
They made a bright start and took the lead after just six minutes when Chris Humphrey’s ball from halfway went past Joe Garner and through to Beckford, who cooly chipped over Tommy Lee.
Chesterfield looked nervy in possession but they managed to weather the rest of the early storm and eventually got a foothold in a lively contest.
There were a few physical confrontations and Gary Roberts was perhaps fortunate to escape without any punishment for grabbing Paul Gallagher around the throat.
Despite controlling the play, chances were few and far between for Chesterfield, with Preston keeper Sam Johnstone only called upon to save a shot late in the half from Dan Gardner.
Tempers threatened to boil over early in the second half and the referee produced yellow cards for Gallagher and Jimmy Ryan after a clash, although Ryan could have seen red after appearing to catch the Preston man with an elbow.
Chesterfield continued to dominate possession and Roberts dragged a shot wide after showing neat footwork to get into the box.
But Preston remained solid at the back and had a good chance of their own when Joe Garner played in Beckford and he shot tamely at Lee.
The Spireites keeper appeared to injure his ankle while making the save and hobbled around his area for the next few minutes before going down to receive treatment.
With no back-up on the bench, home hearts were in mouths, but Lee eventually got to his feet to continue.
Chesterfield’s best opportunities came late in the game but Johnstone palmed out a shot from Roberts and Banks could not hit the target from Clucas’s cross.