Nathan Redmond helped lift Southampton to a 2-0 half-time lead, with the Premier League side looking comfortably in the fourth round before two defensive lapses levelled proceedings.
Jack Marriott and Tom Lawrence would score within three minutes of one another to cancel out Southampton’s lead.
Mohamed Elyounoussi had Saints’ best chance to restore the lead when he was left unmarked on the edge of the six-yard box only to head straight into the goalkeeper’s grasp.
Redmond forced Kelle Roos into a low save at his near post in stoppage time, before Derby County had a chance to book its place in the fourth round at the other end.
A quick break led to David Nugent springing Marriott on goal, but the effort was lifted over the bar with Jannik Vestergaard applying the pressure.
Derby County: Roos, Bryson, Tomori, Keogh, Lawrence (Waghorn 81), Marriott, Evans, Holmes (Jozefzoon 88), Lowe, Bogle, Bird (Nugent 52).
Unused subs: Carson (GK), Wisdom, Mount, Huddleston.
Goals: Marriott (58), Lawrence (61).
Bookings: Bryson (64), Marriott (87).
Southampton: Gunn, Targett, Stephens, Vestergaard, Cedric, Slattery, Ward-Prowse, Elyounoussi (Barnes 71), Redmond, Long, Austin (Johnson 79).
Unused subs: McCarthy (GK), Ramsay, Valery, Bednarek, Romeu.
Goals: Redmond (4, 48).
Bookings: Elyounoussi (33).