The Lilywhites simply weren't good enough on the afternoon, the hosts the better side without having to really produce a sparkling performance.
They were second best in most areas and a miserable game was compounded when skipper Alan Browne was sent-off in stoppage-time.
Browne was shown a second yellow card, followed by red, after getting embroiled in a mass coming together of players.
After all the build-up to the first derby between the sides for more than eight years, what North End served-up was poor.
Blackpool took a 28th minute lead through Keshi Anderson, his low shot inside the box wrong-footing Daniel Iversen at the near post.
It was an advantage doubled in the 68th minute, shortly after PNE had switched from 3-5-2 to 4-4-2.
Gary Madine turned home a low cross from Jerry Yates to seal the home side's victory.
North End's best chance had come two minutes into the second half with the scoreline 1-0.
They broke up field four on one, Emil Riis' cross fired wide by Ben Whiteman with just the keeper to beat.
North End's starting XI was unchanged from Wednesday night's win over Coventry. On the bench, Sean Maguire returned from a hamstring injury to replace Josh Murphy.
The first few minutes were played at a frantic pace with the hosts looking for a quick breakthrough.
Ryan Wintle had an early shot which cleared the bar.
PNE's first chance came in the fifth minute, Ben Whiteman's shot from 25 yards gathered at the second attempt by keeper Dan Grimnshaw.
Browne saw a shot hit the back of a defender after Whiteman's corner had been cleared into his path.
In the 24th minute, a North End counter attack involving Brown, Riis and Daniel Johnson, saw the keeper slide to the floor to block as Johnson closed in - Riis' pass having given him a bit too much to do.
The home side opened the scoring in the 28th minute, A ball from the back found James Husband in plenty of space down the left-wing.
Sepp van den Berg was caught in two minds whether to engage Husband or tuck in to cover in the middle.
Husband pulled the ball back to Anderson just inside the box, his low side-foot shot wrong-footing Iversen and rolling in at the near post.
North End were short of ideas going forward, attempts to get Riis in behind not bringing any joy.
Late in the first half Richard Keogh headed over the hosts, then at the other end, Andrew Hughes' shot was blocked by Marvin Ekpieta in the box.
In the opening exchanges of the second half, both sides had great chances on the counter-attack.
PNE were caught up field after a corner in the 47th minute, the home team getting four against one as they moved into the visitors' half.
Bowler's pass put Anderson clear in the box and Josh Earl got back with a superb covering tackle to take the ball behind for a corner.
North End cleared that flag kick and burst up field, outnumbering their opponents back line.
Riis got away down the right and sent over a low cross to pick out Whiteman in the box who guided a first-time shot wide of the far post.
PNE changed approach in the 64th minute, switching from 3-5-2 to 4-4-2.
Johnson and Josh Earl - slightly unluckily - came off to be replaced Tom Barkhuizen and Maguire.
But within four minutes of the double substitution, North End conceded a second.
Jerry Yates got time on the edge of the box to thread a low ball into the middle, Madine stretching to get his foot to it and guide a shot past Iversen.
It took North End until the 85th minute to create a chance of note after the second goal, Maguire's shot on the turn from Barkhuizen's lay-off, just clearing the bar.
The game ended in unsavoury fashion in stoppage-time, a foul on Maguire seeing players from both teams coming together.
Browne was one of those to pile-in and when things had been calmed down, referee Tom Robinson showed him a second yellow card of the afternoon followed by red.
With it went any remote chance of making the last couple of minutes interesting, North End well beaten on the day.
Blackpool: Grimshaw, Gabriel, Ekpieta, Keogh, Husband, Bowler (Mitchell 88) Wintle, Dougall Connolly 83) Anderson, Madine, Yates (Carey 78). Subs (not used): Moore, Dale, Garbutt, Sterling.
PNE: Iversen, Storey, Bauer, Hughes, Van den Berg, Whiteman (Potts 74), Browne, Johnson (Barkhuizen 64), Earl (Maguire 64_, Sinclair, Riis. Subs (not used): Rudd, Cunningham, Lindsay, Ledson.
Referee: Tim Robinson (West Sussex)
Attendance: 13,946 (2,200 PNE)
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