The 20-year-old, on loan from Watford, scored a fine solo effort five minutes from time after Barry Corr had equalised for Southend eight minutes into the second half.
Dean Morgan had given Wycombe hope of ending their own run of back-to-back defeats after pouncing in the seventh minute, but it wasn't to be for the Chairboys.
Morgan gave Southend warning that he might find the net four minutes before he actually did as he latched onto Sam Wood's through ball and shot wide.
He didn't make the same mistake in the seventh minute though, with Matt McClure this time the provider and Morgan coolly slotting into the bottom-right corner.
Corr then pulled Southend level in the 53rd minute by tapping home Ryan Cresswell's header across goal from a Kevan Hurst corner.
Anthony Straker then struck the crossbar for the Shrimpers and Corr twice went close before Assombalonga fired home the winner after 85 minutes.
