Goals from Neil Danns, Mark Cullen and Andy Taylor secured the three points against a youthful and inexperienced Orient side who had nothing to play having already been relegated to non-league.
The visitors had briefly threatened a comeback when Jens Janse scored at the start of the second half to make it 2-1, but Taylor put the game beyond doubt.
The Seasiders will now take on Luton Town in the play-offs, with the first leg taking place at Bloomfield Road on Sunday, May 14.
The return leg will take place the following Thursday.
The game was forced to start five minutes late due to some disruption outside the main entrance of Bloomfield Road.
The ground was forced into lockdown for around 10 minutes while the Judgement Day 3 protest took place outside, leaving hundreds of Orient fans forced to queue outside.
When they were eventually allowed in, they saw a fairly cautious start from both teams.
The returning Kyle Vassell had the first chance of the day when he was played in by strike partner Mark Cullen but he could only shoot straight at keeper Sam Sargeant.
Cullen himself then came close with a close-range header which he could only nod wide after Kelvin Mellor had swung in a beautiful cross from the right.
The inexperienced Orient players were struggling to get out of their own half and it was clear it was only a matter of time until Blackpool opened the scoring.
Indeed, there were just 11 minutes on the clock when Neil Danns directed his header in the top corner from Jack Payne’s pinpoint cross.
The one-way traffic continued in the same direction with Cullen and Brad Potts both going close with ambitious efforts from range.
It took until the 28th minute for Orient to produce their first cross in the Blackpool box, and even then it was headed away by Clark Robertson under no real pressure.
After a brief lull in the game, the Seasiders eventually bagged their second through Mark Cullen - who took advantage of some lax defending to drill into the bottom corner from 20 yards out.
Pool were almost caught out towards the end of the first half when Callum Kennedy tried his luck from a free kick around 40 yards out, with Sam Slocombe forced to scurry across his goal to tip wide.
But the last chance of the half came Pool’s way, with Tom Aldred stabbing narrowly wide after a corner had dropped to him in the six-yard box.
Bowyer’s men carried on from where they left off at the start of the second period, with Potts shooting straight at the Orient keeper after some intricate work between himself and Kyle Vassell in the build up.
But a minute later the visitors defied all the odds to pull one back after Jens Janse took advantage of Andy Taylor’s slip to latch onto a through ball and shoot through Slocombe’s legs.
Clearly Orient hadn’t read the script.
Pool’s two-goal lead should have been restored just minutes later but Potts somehow managed to blaze over after being found unmarked about eight yards out.
Kyle Vassell then came close with a drilled effort from the edge of the box which Sargeant stopped with a strong hand.
That elusive third eventually came in the 65th minute, when Andy Taylor drilled home into the far corner after playing a quick one-two with Cullen.
At that point, the Seasiders knew their job had been done and decided to put on the handbrake and see out the rest of the game, although Kyle Vassell perhaps should have done better with two chances in stoppage time.
All eyes will now turn to the two-legged tie against Luton, a side who did the double over Bowyer’s men this season.
Blackpool: Slocombe, Mellor, Aimson, Aldred, Robertson, Taylor, Payne, Danns (Black), Potts (Flores), Cullen (Gnanduillet), Vassell
Subs not used: Lyness, Osayi-Samuel, Delfouneso, Philliskirk
Leyton Orient: Sargeant, Janse, Clark, Pollock (Happe), Kennedy, Collins, Ochieng, Alzate, Moncur (Adeboyejo, Semedo, Abrahams (Koroma)
Subs not used: Janata, Perkins, Alderson, Dalby
Referee: David Webb
Attendance: 3,602 (951 Orient)