Nicolas Anelka’s 11th goal of the season set Carlo Ancelotti’s team on their way before Daniel Sturridge added the second, the 20-year-old’s third goal in his last two games.
It was the perfect response after Carlo Ancelotti’s side had lost their place at the top of the Premier League table in midweek.
Yet the outcome might have been different had Preston midfielder Darren Carter not spurned a glorious chance from three-yards when the score was 1-0.
Chelsea are looking to become the first team to defend the FA Cup since Arsenal mounted a successful defence of the competition in 2003.
Ancelotti took the unusual step of revealing his starting line-up on the eve of the tie, the Italian opting to make six changes to the side which hammered Sunderland 7-2 last Saturday.
Portuguese keeper Hilario and Sturridge were among those handed a rare start although key players Frank Lampard, John Terry and Nicolas Anelka were also on duty against the Championship club.
Preston are languishing in the bottom half of the second tier after losing their last three league games.
Yet the hosts gave as good as they got in the opening exchanges, Chris Brown causing panic inside the Chelsea defence after getting on the end of Chris Sedgwick’s eighth minute cross.
Chelsea, who thrashed Preston’s league rivals Watford 5-0 in the previous round, took a while to get into their stride.
Keeper Andy Lonergan did well to deny Russian midfielder Yury Zhirkov in the 16th minute before Chelsea had a goal disallowed in controversial circumstances.
Moments after Lampard had been fouled on the edge of the area, substitute Florent Malouda had the ball in the back of the net only for referee Mike Dean to rule it out and award Chelsea a free kick for the illegal challenge on their midfielder.
Chelsea were beginning to build some momentum, Lonergan beating away a fiercely struck free-kick by Alex before Anelka found the vital breakthrough in the 36th minute.
The former Manchester City and Arsenal forward made it five goals in four games following an excellent low finish from an angle after getting the better of Youl Mawene, defender Sean St Ledger blocking the view of his keeper and deflecting the ball into the net.
Yet despair doubled four minutes later when they spurned a glorious chance to equalise, Carter slicing the loose ball over the bar after Hilario parried Brown’s strong header.
It was a stunning miss and one that ultimately proved Preston’s downfall as Chelsea doubled their advantage within three minutes of the restart.
A corner by Malouda was met by Terry whose header was kept out by Lonergan. However, the rebound fell to Sturridge who made no mistake from close range.
To their credit, Preston continued to battle but Chelsea should have won by a more handsome margin.
Michael Ballack was denied by a fine Lonergan save while Lampard also went close before the England midfielder was replaced by Joe Cole.
Deco, who has appeared on an infrequent basis under Ancelotti, bossed the midfield well as Chelsea produced a professional performance.
Sturridge was unfortunate not to add his second goal when his fierce 20-yard effort whistled narrowly wide in the 72nd minute. (SW/MG/rex)