Yohan Cabaye scored the only goal of the game as the north-east club beat United in their own backyard for the first time since 1972.
Newcastle have now won five of their last six Premier League games and will be striving for a fourth consecutive win at St James’ Park when Southampton make the long journey north.
Pardew was sacked by Southampton when they were in League One three years ago and the 52-year-old is expecting a stern test against his former employers.
He said: "We’ve had a really strong period and it’s important we focus on this game.
"There is a huge significance in this result. Southampton are a good side, very similar to ourselves in that they are set up to attack, it should be a cracker.
"We didn’t slip up against Norwich and West Brom, and this is a game we’re really looking forward to."
France midfielder Cabaye will not feature against Mauricio Pochettino's side after picking up his fifth booking of the season against United.
Mathieu Debuchy has recovered from a dead leg sustained at Old Trafford, so Ryan Taylor (knee) is their only other absentee.
St James' Park has not been a happy hunting ground for Southampton, as they have not won there since 1997.
Newcastle have won nine of their last 10 home games against Southampton and Pochettino's men have failed to win on the road since their 1-0 victory at Liverpool in September.
The St Mary's Stadium club managed to stop the rot with a 1-1 draw against Manchester City last weekend as Pablo Daniel Osvaldo scored his second goal in as many games and they will replace Newcastle in seventh place with a win on Saturday.
Pochettino said: "Newcastle are a team who have - in the last few weeks - been playing well.
"They are a physical, strong, aggressive side who are tough to beat. We are aware what we're up against."
Pochettino revealed Morgan Schneiderlin (groin) could play some part, but the midfielder is not fit enough to play the whole game.
Nathaniel Clyne (hamstring), Victor Wanyama (leg), Artur Boruc (hand), Kelvin Davis (back), Danny Fox (hamstring) and Guly Do Prado (knee) are definitely out.
