The encounter on Saturday evening will rekindle memories of Saints' infamous giantkilling in 1976, when Bobby Stokes' solitary goal saw second-tier Saints overcome top-flight United in the final.
On Saturday the two teams come together in another David versus Goliath encounter, although this time a further division separates the two sides.
Southampton go into the match off the back of a goalless draw with Notts County and a 2-0 defeat at Tranmere, while United are in the midst of an imperious unbeaten run in the Premier League.
Despite the differing fortunes, Chaplow insists Saints do not feel any pressure and, if anything, believe it could boost their tilt at promotion from npower League One.
"We're all really looking forward to the game," said Chaplow. "Obviously Manchester United need no introduction and hopefully we can put on a good spectacle.
"We take every game as it comes. We're very level as a group and down to earth.
"Things haven't gone for us in the last couple of games and we've got the hype now of a game against Manchester United, but we're going to keep our focus on the league as well.
"It takes a bit of pressure away from the league where we're expected to win more games than we lose or draw and we're looking to get promoted so there's pressure on us in the league.
"But on Saturday it's flipped around a bit and we're just looking forward to going out and enjoying ourselves.
"It'll be no different for us as we'll approach it in the same way that we do every game."
Chaplow, who made his loan move to St Mary's permanent earlier in January, believes Saints have a chance of usurping the Premier League leaders thanks to their blend of wily old-timers and precocious youngsters.
"We're a professional group - the gaffer's got us working really hard, so we'll approach it right and if things come off for us on the day you never know," he said.
"Out of the lads that we've got at the minute there's a mix of youth and old, and I'm sure that the experienced lads will pull the younger ones through it.
"The thing with being young is that you've not got any fear - you can go out there enjoy it, get on the ball and express yourself, so it's up to the older lads to keep everyone talking on the pitch and make sure we're all together."
Chaplow is one of a handful of players in the Southampton ranks with experience of facing United and believes ties like this one will only fuel the club's determination to return to the big time.
"These are the games that the club wants and it's where we need to be again, playing against the Manchester Uniteds, the Chelseas, and the Tottenhams," he added.
"It's where the club used to be and where it's striving to be again, so it will be nice to welcome Manchester United to St Mary's once more, and hopefully we can put on a good performance and give the fans something to cheer about.
"It'll be a good game, and you always want to get one over on any Premier League side, whoever you're playing against.
"I can say that the lads are going to look forward to playing against them with a smile on our face, and if things come off for us then we can produce a result."