Howard struck twice inside 22 minutes either side of half-time to cancel out Andrew Surman's seventh-minute opener to give Derby a one-goal advantage ahead of Tuesday's return leg at Pride Park.
Surman gave Southampton a dream start when he rattled in his fifth goal of the season with an unstoppable right-footed curler from 20 yards.
But Howard drew the visitors level nine minutes before the interval with a towering back post header from Southampton old boy Matt Oakley's cross.
Marek Saganowski should have restored Saints' lead just two minutes later when he rammed a shot against the crossbar from the edge of the area after racing on to Djamel Belmadi's centre.
Referee Michael Jones dished out six yellow cards in a fiercely contested first half, with Dean Leacock, Stephen Pearson, Oakley and Seth Johnson booked for Derby and Surman and Pedro Miguel Pele for the hosts.
Central defender Pele gifted Derby the chance to take the lead in the 58th minute when he clumsily tripped Scottish winger Pearson on the right-hand edge of the box.
The referee had no hesitation in awarding a penalty and man-of-the-match Howard sent the 3,000 travelling fans into raptures when he calmly slotted the ball into the bottom left-hand corner of the net.
Howard, who has now scored 19 goals for Derby since last summer's move from relegated Luton Town, also notched the winner in the Rams' 1-0 victory at St Mary's in February.
Former Manchester City striker Jonathan Macken came within inches of putting the tie to bed when he struck a post with a 20-yard pile-driver.
Saganowski was chosen ahead of Southampton's two-goal final day hero Leon Best and 20-goal top scorer Grzegorz Rasiak.
He wasted a glorious chance to level the tie 20 minutes from time when he smashed a 20-yard shot against the underside of the crossbar after Belmadi had broken free from the left and whipped in a teasing cross.