It looked like more of the same for the Blues, who fell behind to James Norwood’s emphatic first half striker.
But Tom Naylor nodded the hosts back on level terms before the break and Marcus Harness slotted home the winner after it.
Cowley’s first starting line-up saw two changes from the side that were narrowly beaten at Peterborough earlier in the week.
Jordy Hiwula and Marcus Harness both returned, with Ben Close and Rasmus Nicolaisen dropping to the bench.
After playing with three at the back against Posh, there was also a switch to a 4-2-3-1 system, with Ryan Williams tucked in behind Hiwula.
There were a couple of familiar faces in the opposition technical area, with Paul Cook and Gary Roberts leading the Tractor Boys.
Ronan Curtis had an early attempt, courtesy of a 35-yard free-kick that was bent over the wall, but comfortably into the arms of Tomas Holy.
There was plenty of noise being generated by both managers, as well as the injured John Marquis up in the South Stand.
It was not a particularly rip-roaring contest on the pitch, though, with both sides showing plenty of energy, but failing to turn that into clear-cut chances.
Ipswich’s first opportunity also came from a free-kick, with Jack Whatmough booked for his challenge on Keanan Bennetts.
Andy Cannon adopted the now popular ‘draught excluder’ technique by laying down flat behind the wall.
Alan Judge bent his strike over it, however, and Craig MacGillivray flung himself to the left to push the ball clear.
But the visitors did break the deadlock soon after, as Norwood raced onto Gwion Edwards’ threaded pass and rifled home.
Pompey quickly fought back, though, and levelled by scoring their first goal in 358 minutes of football.
Curtis whipped a fine corner into the box and NAYLOR rose highest to send a header against the inside of the post and into the net.
Ipswich Town 1
An early long-range attempt from Edwards straight after the restart was easily dealt with by MacGillivray.
The Blues then came close to taking the lead for the first time in what would have been a similar goal to their first.
Naylor again met a corner from Curtis, but this time Holy was able to push the ball away – then stop Sean Raggett from converting the rebound.
Cowley made his first switch just before the hour mark, with Andy Cannon – who had just been booked – making way for Close.
Williams then had a chance after being picked out by Harness following a quick break, but could not keep his angled strike on target.
A second switch followed on 72 minutes, with Michael Jacobs on for Hiwula and Curtis moving up front.
And it was the Republic of Ireland international who provided the pass for Pompey’s second goal a few seconds later.
He sent a low pass across the area and HARNESS’ first shot was blocked by Judge, but the ball landed back at his feet to slam past a helpless Holy.
Pompey looked to keep possession as much as possible in the closing stages, but had two late chances to increase their lead.
Toto Nsiala almost sliced a Harness cross into his own net and then, from the resulting corner, Holy kept out James Bolton’s header from point-blank range.
But the Blues saw out five minutes of stoppage-time to collect a precious three points and ensure the Cowley brothers began their reign with a win.
Pompey (4-2-3-1): MacGillivray; Bolton, Whatmough, Raggett, Brown; Naylor (c), Cannon (Close 58); Harness, Williams, Curtis; Hiwula (Jacobs 72)
Goals: Naylor 41, Harness 72
Booked: Whatmough, Curtis, Cannon, Jacobs
Subs not used: Ward, Mnoga, Nicolaisen, Daniels, Byers
Ipswich (4-2-3-1): Holy; Chambers (c), Nsiala, Wilson (Vincent-Young 79), Ward; Bishop (Parrott 89), Dozzell; Edwards, Judge (Jackson 79), Bennetts (Dobra 59); Norwood
Goals: Norwood 32
Booked: Edwards, Chambers, Bishop
Subs not used: Cornell, McGuinness, Skuse
Referee: Alan Young