Debutant defenders Christian Dailly and Miguel Llera netted either side of a fine Nicky Bailey strike to spoil the newly-promoted Chairboys' own League One return.
Dailly, 35, headed home Jonjo Shelvey's 21st-minute corner and skipper Bailey found the top corner two minutes later thanks to good work from another new recruit, Frazer Richardson.
Wycombe were back in it two minutes before the break when Chris Zebroski headed in Craig Woodman's cross at a time when Llera was off getting a head wound bandaged.
The Spaniard returned to make it 3-1 five minutes after the restart when Wycombe striker Matt Harrold's misguided clearance of Shelvey's free-kick allowed an easy close-range finish.
Zebroski's smartly-taken second set up an exciting finish but Charlton held on for the final 17 minutes, with Bailey and Richardson making goal-line clearances to deny the striker his hat-trick.
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