Michael Tonge scored for the second game in a row but ten man Vale were undone by a hat-trick from Samuel Sáiz at Elland Road.
Michael Brown made a number of changes as Anton Forrester started as a lone frontman while Billy Reeves, Dan Turner, Rekeil Pyke and Joe Davis all started.
After a quiet start, it was the home side who took the lead through a good effort from Sáiz on twelve minutes but the Valiants equalised against the run of play when Tonge netted against his former club on 36 minutes. It was all-square at the break but Vale were forced into a change as Sam Hornby made his first-ever senior appearance replacing the injured Rob Lainton.
Hornby was soon pressed into action and made a number of saves before a quickfire double from Sáiz on sixty and sixty minutes made it comfortable for the home side. Brown brought on Tom Pope and Marcus Harness but Ekuban made it 4-1 with seven minutes remaining and Vale were heading out of the cup at the first round.
Vale’s night was made even worse when left-back Gavin Gunning picked up a late second yellow card and was sent-off in the closing minutes. The Valiants will now potentially face Wycombe in their first home game without their first-choice goalkeeper and left-back.
Vale: Lainton (Hornby 45), Davis, Smith, Kay, Gunning , Reeves, Tonge, Pugh ( Harness 65), Turner, Pyke, Forrester ( Pope 82 )
Subs: Gibbons, De Freitas, Calverley, Whitfield