Carlton Morris opened the scoring for the Rams before half-time to put a now 17-game unbeaten run at risk, but Leo Scienza equalised around the hour.
The Brazilian’s curling effort was his seventh goal of the league season, and set the stage for Taylor Harwood-Bellis to head the winner shortly after.
It helped Saints leapfrog Hull City, who were beaten by Sheffield United, up to fifth in the table, three points behind Middlesbrough with a game in hand.
The result means February and March’s manager of the month, Tonda Eckert, boasts the best record of any Championship boss since he was appointed.
Keeping up the pressure on the teams above. Blackburn here on Tuesday. 👌#SaintsFC pic.twitter.com/OHerbqqIcR
— Alfie House (@AlfieHouseEcho) April 11, 2026
Saints drew 1-1 at Derby under Will Still in October, with the impressive Rams coming to St Mary’s eighth in the table, just three points behind Saints.
Eckert made four changes from Tuesday’s 5-1 win at Wrexham, with Caspar Jander, Tom Fellows, Leo Scienza and Ross Stewart back in the XI.
Derby were already without key forwards Patrick Agyemang and Ben Brereton Diaz, unavailable against Saints, before Bobby Clark was forced off.
The hosts had early chances, but Fellows could not get his touch right in good space before Finn Azaz pulled wide of the post from inside the box.
Scienza and Ryan Manning attempted 11 crosses, more than the rest of the two teams combined, by the 38th minute, but not one was completed.
That was when Derby took the lead with a cross of their own, after Azaz gifted a corner-kick, which fell to Morris for his 12th goal of the league season.
The delivery was inadvertently flicked on by Jander as he challenged for a header, and the former Luton man arrived at the back-post to turn home.
Stewart struck into his own standing foot with another chance before the break, but despite boasting 65 per cent possession, Saints were trailing.
Eckert sent his players out from the team talk minutes early. His messages were clear, as were Eustace’s, with yellow cards starting to follow Derby.
Fellows headed over the bar after doing well to get to a cross, before Scienza curled a beautiful effort into the far corner to equalise after 62 minutes.
Jander’s drive helped create the chance, as he played across the field to Azaz, who slotted the Brazilian in with plenty of work to do left of the box.
And defender Harwood-Bellis completed the turnaround seven minutes later, directly heading Saints ahead from a Manning free-kick into the area.
His goal was his sixth of the Championship season; A vital contribution from the man for whom Saints rejected January transfer bids from West Ham.
Harwood-Bellis followed that up with a crucial block on Morris up the other end, and Saints held on for the time remaining to keep their run going.
Saints could have scored a third, but Cyle Larin missed his opportunity to shoot after Flynn Downes elected to play him with options ahead of him.
Saints: Peretz; Bree (Wood, 87), Harwood-Bellis, Stephens, Manning; Downes, Jander, Fellows (Matsuki, 63), Azaz (Charles, 75), Scienza (Edozie, 75); Stewart (Larin, 63).
Unused subs: Long, Welington, Bragg, Archer.
Booked: Larin.
Derby County: O’Donnell; Johnston (Forsyth, 65), Clarke, Sanderson, Ward, Ozoh (Langas, 65), Travis (Salvesen, 83), Clark (Fraulo, 8), Szmodics, Banel (Eames, 65), Morris.
Unused subs: Vickers, Batth, Gordon, Allen.
Booked: Ozoh, Fraulo.
Referee: Andrew Kitchen.