Vaughan, who joined the Terriers from Norwich in the summer following a successful loan spell last term, netted his ninth goal in as many outings to keep Chris Powell's side waiting for their first points on the road.
The 25-year-old's first-half strike set the home side on their way before defender Joel Lynch fired home a stunning second.
Cameron Stewart netted an equally fine consolation for the visitors.
Town boss Mark Robins made three changes to the side held to a goalless draw by Doncaster on Saturday, with Paul Dixon, Sean Scannell and Jonathan Stead all recalled to the starting line-up.
Powell made just one change to the Addicks side that also drew against Watford at The Valley, Marvin Sordell replacing the injured Yann Kermorgant.
Robins was almost first to reap the rewards of a reshuffle when veteran striker Stead fired just wide after Addicks keeper Ben Hamer failed to hold a dangerous cross.
Scannell twice went close soon after as the hosts continued to stretch a ragged-looking Charlton defence.
And all eyes were on referee Stuart Attwell when centre-back Dorian Dervite felled the apparent goal-bound Vaughan. But, following a brief consultation with his assistants, Attwell only produced a yellow card, having deemed it not to be a goal-scoring opportunity.
It took the visitors until the stroke of half-time to record their first effort of the game, Simon Church's header well held by Alex Smithies.
But the Terriers had the final word of the half as Adam Hammill picked out Vaughan in the final few seconds to head home the club's 2000th goal in England's second tier.
Despite losing Jonathan Hogg to injury shortly after the restart, Town continued on the front foot as Stead fired just wide following a neat interchange with striker partner Vaughan.
Full-back Lynch was rather more clinical just after the hour mark when he collected the ball 35 yards from goal and, urged by the home supporters to shoot, rifled an unstoppable strike into the top corner of Hamer's goal.
Addicks substitute Stewart ensured a nervy final 10 minutes when he cut inside and fired a looping long-range effort over the head of Smithies to stun the home supporters.
Powell also introduced Callum Harriott as the visitors launched a siege on the Huddersfield penalty area in the final minutes.
First Smithies did well to block Bradley Pritchard's fizzing effort before Lawrie Wilson fired just wide as the Terriers held out for a hard-fought three points.