Chesterfield had defender Sam Hird sent off in the third minute tonight - and never recovered.
A pass was lofted over his head and just before Joe Garner could go through, the Doncaster-born centre half fouled him.
The ref deemed it a clear goal-scoring opportunity and it was a straight red for Hird.
Paul Cook, the manager, made a swift tactical change: Charlie Raglan coming on for Daniel Jones.
PNE hit the post from a corner with Chesterfield still in some disarray.
But gradually they began to compose themselves and looked dangerous at set-pieces.
However, the Lancashire side took the lead on 29 minutes when Garner headed a cross neatly into the bottom right-hand corner.
On 52 minutes Sam Morsy smashed in a 25 yarder, but it was caught cleanly by Sam Johnstone.
North End started to threaten, again, although a Sam Clucas cross for Byron Harrison caused some discomfort in the away ranks.
Harrison had a clear chance to level on 66 minutes, but he fired over from six yards.
Preston confirmed ownership of the points when Garner - such a danger all night - doubled their advantage with a header from a corner, on 78 minutes.
*Spireites started off the night in five place, one spot but eight points behind North End.
Chesterfield (4-4-2): Lee, Darikwa, Evatt, Hird, Jones, O’Shea, Morsy, Ryan, Clucas, Lavery, Harrison.
Subs: Chapman, Humphreys, Raglan, Dieseruvwe, Banks, Duffy, Ariyibi.
PNE (3-5-2): Johnstone, Wright, Clarke, Huntington, Wiseman, Welsh, Johnson, Gallagher, Laird, Davies, Garner.
Subs: Stuckmann, Humphrey, Kilkenny, Buchanan, Reid, King, Ebanks-Blake
Ref: Peter Bankes (Merseyside)
Attendance: 6,309, (458 away fans)