Shrewsbury were relegated from the third tier last season and are currently looking well-placed to make an immediate return, sitting in third.
Southern is keen to help that promotion push as he prepares for his debut against Stevenage.
The 33-year-old made 21 Premier League appearances for Blackpool during the 2010-11 season, before leaving the club for Huddersfield Town in June 2012, and he is confident that he has a lot to contribute.
He told the club's official website: "I've been there and done it, and I'm chomping at the bit to get some football under my belt.
"I'm looking forward to helping in any way I can to what is already a successful squad and a successful season so far.
"Obviously the lads who are playing have done really well, [but] I can bring some experience and a steady head in the middle of the pitch."
Aiming to retain their status as table-toppers, however, are Wycombe Wanderers, with manager Gareth Ainsworth hoping to celebrate his new five-and-a-half-year contract by beating Mansfield Town on the road.
Burton Albion go into the weekend a point behind the pacesetters and will be expected to extend their seven-match unbeaten run at York City, who have lost their last two games.
At the other end of the table, Tranmere Rovers can move three points clear of the relegation zone with a win over visitors Hartlepool United, who are nine points adrift at the bottom, while Carlisle United will be looking to build upon last week's triumph over AFC Wimbledon when they head to Bury.
Luton Town, in fourth, head to Cheltenham Town looking to capitalise on any potential Shrewsbury slip-up, with Newport County – facing Northampton Town away from home – also on 46 points.
Portsmouth, who have not won any of their last seven, face the prospect of sixth-placed Southend United visiting Fratton Park, while play-off hopefuls Exeter City could leap back into the top seven if they take all three points from their trip to Oxford United.
AFC Wimbledon and Accrington Stanley go head-to-head at Kingsmeadow and Plymouth Argyle entertain Morecambe.
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