The Shrimpers reserves were unable to create clear cut chances and were ultimately undone by a long-range strike from Jake Hide.
The home side enjoyed their best spell of possession at the start of the match and, with seven minutes on the clock, James Walker swapped passes with Stuart O'Keefe before unleashing a low, 20-yard drive which was tipped around the left post by Jamie Young.
Damian Scannell then volleyed a deep Duran Reynolds cross wide of the left post before the visitors came back into the game with Jordan Lumsden sending a well-struck 20-yard shot inches over the crossbar.
Wycombe striker Hide was then denied by Ian Joyce after breaking the offside trap and, in the 23rd minute, Lumsden headed wide of the right upright from 12 yards.
The Chairboys continued to pile on the pressure and, with 30 minutes on the clock, they opened the scoring as Hide spotted Joyce off his line and directed a long range effort into the top left hand corner of the South Stand net.
At the start of the second half, Ashton sent a 30-yard shot fizzing past the right post but the Shrimpers responded with the hard-working Charles Ademeno cut in off the left flank and dragged a low effort just off-target.
Walker then forced Young into action with a curling effort from the edge of the area but it was his opposite number, Joyce, who was called upon next as he smartly palmed away a close range effort from Scott Shulton.
Southend attempted to get back into the game by bringing on promising 16-year-old Justin Hazell for his reserve team debut in the 78th minute.
He replaced Ademeno on the left flank but Blues were unable to conjure up a late equaliser as Stuart O'Keefe's last gasp effort was scrambled to safety by Leon Crooks after Young had fumbled a deep, left wing cross from Reynolds.
Southend United: Joyce, Forshaw, Sankofa, Reynolds, Morris (Jones 71), Scannell, Lokando, O'Keefe, Ademeno (Hazell 78), Furlong, Walker. Subs not used: Henry, McDonald & Calver.