The Seasiders, who started with five debutants, took the lead after 19 minutes when new signing Kyle Vassell was played through by another debutant Colin Daniel and netted from 12 yards via a deflection from keeper Bobby Olejnik.
But Exeter should have been level five minutes later as Lee Holmes picked out Ollie Watkins, who could only put a diving header on to the post from two yards with the goal gaping.
The woodwork denied Exeter for a second time after 44 minutes, as Jake Taylor's flick came back off the inside of the far post before Watkins had a header saved by Sam Slocombe.
Blackpool's new keeper Slocombe produced a sensational reflex save to prevent an Andy Taylor own goal six minutes after the break but, straight down the other end, Troy Brown was not so fortunate as he deflected Brad Potts' cross past Olejnik to ensure a Blackpool victory.
Report supplied by the Press Association.
Match ends, Blackpool 2, Exeter City 0.
Second Half ends, Blackpool 2, Exeter City 0.
Corner,  Exeter City. Conceded by Brad Potts.
Attempt blocked. Ryan Harley (Exeter City) right footed shot from the left side of the box is blocked.
Liam McAlinden (Exeter City) wins a free kick in the defensive half.
Foul by Will Aimson (Blackpool).
Attempt missed. Mark Yeates (Blackpool) left footed shot from outside the box is too high.
Attempt blocked. Mark Yeates (Blackpool) left footed shot from outside the box is blocked.
Attempt saved. Jordan Moore-Taylor (Exeter City) header from the centre of the box is saved in the bottom right corner.
Corner,  Exeter City. Conceded by Will Aimson.
Corner,  Exeter City. Conceded by Will Aimson.
Attempt blocked. Ollie Watkins (Exeter City) right footed shot from the left side of the box is blocked.
Attempt blocked. Danny Pugh (Blackpool) left footed shot from the centre of the box is blocked.
Foul by Ryan Harley (Exeter City).
Kelvin Mellor (Blackpool) wins a free kick in the defensive half.
Attempt missed. Mark Yeates (Blackpool) right footed shot from the right side of the box misses to the right.
Attempt missed. David Wheeler (Exeter City) left footed shot from the centre of the box is close, but misses to the left.
Foul by Brad Potts (Blackpool).
Jake Taylor (Exeter City) wins a free kick on the right wing.
Corner,  Exeter City. Conceded by Kelvin Mellor.
Foul by Jim McAlister (Blackpool).
Lee Holmes (Exeter City) wins a free kick in the attacking half.
Attempt missed. Mark Yeates (Blackpool) left footed shot from outside the box is close, but misses to the right.
Jim McAlister (Blackpool) wins a free kick in the attacking half.
Ryan Harley (Exeter City) is shown the yellow card for a bad foul.
Foul by Ryan Harley (Exeter City).
Danny Pugh (Blackpool) wins a free kick in the attacking half.
Foul by David Wheeler (Exeter City).
Attempt missed. Brad Potts (Blackpool) left footed shot from the centre of the box is just a bit too high.
Attempt blocked. Jamille Matt (Blackpool) right footed shot from the centre of the box is blocked.
Corner,  Blackpool. Conceded by Pierce Sweeney.
Attempt missed. Jamille Matt (Blackpool) header from the centre of the box is just a bit too high.
Corner,  Blackpool. Conceded by Jordan Moore-Taylor.
Attempt blocked. Mark Yeates (Blackpool) right footed shot from the right side of the box is blocked.
Substitution, Exeter City. David Wheeler replaces Craig Woodman.
Attempt blocked. Lloyd James (Exeter City) right footed shot from outside the box is blocked.
Corner,  Exeter City. Conceded by Kelvin Mellor.
Hand ball by Brad Potts (Blackpool).
Hand ball by Jamille Matt (Blackpool).
Substitution, Exeter City. Liam McAlinden replaces Robbie Simpson.
After successive relegations, Blackpool won their first game in the fourth tier since 2001 with victory at home to Exeter.