It was a cagey start to the game from Pools as they again took time to get going in the game and the visitors enjoyed the best of the early play.
Myles Weston was a threat down the left with his pace, while Adebayo Akinfenwa offered a constant presence for the visitors in the final third.
Sam Saunders sent a freekick in on goal from the left which was well held by Joe Fryer, while the midfielder curled another freekick from further out, wide of the near post.
Pools did start to offer more on the attack, most notably through Nathan Thomas and Lewis Alessandra.
Thomas crossed in from the left, catching Will De Havilland out but the defender got the ball out for a corner. Alessandra ran in to send a shot at goal from the following corner but his low drive was blocked out by the crowd.
Alessandra was next up to try again, this time showing a great turn to run in and shoot on goal but his effort went over the bar.
Alessandra burst down the left to square a ball into the box for Thomas, where the winger looked to be tripped as he ran into the box. The referee showed no interest in the appeal though and the chance passed.
Wycombe opened the scoring on 24 minutes through Akinfenwa and it was a well-taken effort; the big striker exchanged passes with Dayle Southwell before barging his way into the box and firing a low effort past Fryer to make it 1-0.
Pools went on to have plenty of possession in the remainder of the half, with just the final shot on goal missing.
Thomas put a great cross in from the left which was touched away from Padraig Amond by Jamal Blackman, before the winger twisted into space to shoot from distance but the strike went over the bar.
Brad Walker sent a drive in from 35 yards which went over the bar before the half-time break but it went the same way over target and Pools went into the second half trailing 1-0.
Pools enjoyed a good spell of pressure just after half time, passing the ball neatly around the box before Alessandra took control to shoot at goal, His effort rolled wide of the far post but Pools were playing some nice football.
At the other end, Luke O’Nien fizzed a shot in from outside the box, which went out just wide of Fryer’s right-hand post, as both sides battled for the next goal.
Southwell picked the ball up 25 yards out on goal to power a shot at goal, which called Joe Fryer into action but the Pools stopper did well to get up and tip it over the bar.
Alessandra was at the heart of things for Pools again as they broke forward on 66 minutes; the forward found some space just over the half way line and used his pace well to close down on goal. With Amond to his right, Alessandra took his time before slotting the ball out to the striker, but Michael Woods arrived to join the attack and just touched the ball away from Amond.
Fryer was in action again for Pools just after when he pulled off a great stop to deny Dominic Gape with a testing strike from distance.
Thomas won a corner for his team as they continued to look for the equaliser and Pools went closest to scoring with it, pulling the first real save out of the Wycombe keeper; Scott Harrison rose to meet the corner and his powerful header was kept out by Blackman.
Brad Walker got up to meet another corner in to the box but his looping header bounced onto the crossbar on its way over. And with just ten minutes remaining, Pools had a good spell of pressure with lots of possession around the area but just not that final touch to test Blackman again.
But it was the visitors who had the final word on a frustrating afternoon for Pools as Paris Cowan-Hall cut into the box from the right and sent a strike across Fryer and into the far corner to make it 2-0 on 90 minutes.
So a scrappy game finished in defeat for Pools, who face a trip to take on Blackpool next weekend.
Full Time: Hartlepool United 0 Wycombe Wanderers 2
Booked: Harrison (90)
Attendance: 3356 (159 Wycombe Wanderers)
Pools: Fryer, Richardson, Harrison, Walker, Deverdics, Featherstone, Woods, Hawkins (Rooney 72), Alessandra, Amond, Thomas.
Subs Not Used: Bartlett, Martin, Bates, Hawkes, Orrell, Rodney.
Wycombe Wanderers: Blackman, Jacobson, Pierre (Muller 31), Southwell (Thompson 83), Harriman, O’Nien, Weston, Akinfenwa (Cowan-Hall 55), De Havilland, Gape, Saunders.
Subs Not Used: Richardson, Jombati, Freeman, Jakubiak.