Anthony Stewart scored right at the death to deny Pompey their first victory in more than a month.
The Blues were well below-par in the first half and deservedly went in behind to a Matt McClure strike at the interval.
But they stepped up several gears after the break, although David Connolly missed a chance to level from the spot.
Andy Barcham soon made the Fratton faithful forgot about that, however, as he struck a fine equaliser moments later.
And Agyemang – whose goal against Wycombe in October was wiped out when the match was abandoned – then headed the hosts in front.
But Stewart converted a corner deep into stoppage-time to break Pompey’s hearts.
Andy Awford made one change from the side that drew at Hartlepool on Saturday.
Jack Whatmough missed out with a virus, so Joe Devera moved to centre-back with Danny East coming in on the right.
It was Pompey who were first to threaten when East’s low cross was scuffed goalwards by Ricky Holmes, but Wanderers keeper Matt Ingram got down low to his right to push the ball clear.
The visitors’ early contribution consisted of fouls from Leon Johnson and Matt Spring that saw the duo receive bookings from referee Darren Drysdale.
Chairboys skipper Stuart Lewis did hit a cleanly-struck effort on 20 minutes, but the ball flew straight into Trevor Carson’s arms.
But Wycombe broke the deadlock moments later when McClure swivelled inside the box and drilled a low short into the bottom corner.
Pompey then received a further blow when East was forced off with a nasty-looking injury.
The defender challenged bravely for a header, but landed awkwardly and was stretchered from the field after receiving lengthy treatment.
Bondz N’Gala came on to replace him, taking up position in the centre with Devera moving back to the right-back berth.
The Blues then almost fell further behind, but Carson made a superb save to deny McClure after Dean Morgan had flicked on Spring’s free-kick.
Half Time: Pompey 0 Wycombe 1
Awford made a switch to 4-4-2 at the start of the second half, as Connolly replaced Jed Wallace.
Bur it was still Wycombe looking the more threatening and Dan Potts had to make a decent challenge on 56 minutes after Sonny Bradley had sent his clearance straight into the path of Paris Cowan-Hall.
Pompey did start to look more of an attacking menace as the half progressed, however, and Ingram was called into action to deny Holmes.
Barcham then embarked on a surging run through the centre before eventually being crowded out inside the box.
And Shaun Cooper was next to try his luck on 65 minutes, taking a delicate touch on the edge of the area before drilling a shot narrowly wide.
Pompey were then handed a great opportunity to equalise when Sam Wood felled Connolly in the box and Drysdale pointed to the spot.
Connolly stepped up to take the penalty, but Ingram saved it and Marvin McCoy then made a superb block to prevent Ryan Bird from slamming in the rebound.
But the Blues were not behind for much longer as BARCHAM collected Holmes’ pass and lashed a ferocious shot into the roof of the net.
Awford was not satisfied with just a point, however, making an attacking change on 78 minutes as Agyemang replaced Johnny Ertl.
Pompey were pouring forward and Bird slipped when in a good position before Barcham sent a header wide.
And they forged ahead on 84 minutes when Holmes whipped in a free-kick from the right and AGYEMANG got in front of his marker to glance home a fine header.
Wycombe threw on a couple of substitutions as they tried to salvage something from the game.
One of those was Max Kretzschmar and it was his corner that Stewart converted seconds before the final whistle blew.
Pompey (4-2-3-1): Carson; East (N’Gala 38), Devera, Bradley, Potts; Ertl (c) (Agyemang 78), Cooper; Barcham, Wallace (Connolly 46), Holmes; Bird
Goals: Barcham 72, Agyemang 84
Booked: Wallace, Cooper
Subs not used: Sullivan, Painter, Padovani, Ferry
Wycombe (4-diamond-2): Ingram; McCoy, Doherty, Johnson (Stewart 81), Wood; Lewis (c), Spring, Cowan-Hall, Knott (Kretzschmar 87); Morgan (Kuffour 87), McClure
Goals: McClure 22, Stewart 90+4
Booked: Johnson, Spring, Knott, Ingram
Subs not used: Horlock, Dunne, Arnold, Craig
Referee: Darren Drysdale
Attendance: 14,942 (681 away fans)