All three of the Port's goals came after the break, in the form of sublime strikes from Elliot Osborne and Dion Charles and a Jack Sampson tap-in.
Just as it appeared the Bucks' night could not get any worse, Amari Morgan-Smith was shown a straight red card late on and will miss the next three National League North games.
Rob Edwards' side remain third bottom and have not won on their travels since beating basement boys North Ferriby United 2-0 on October 21.
Southport have set a club non-league record by winning six games in a row at Haig Avenue.
Dom Smith was making his Telford debut, having joined from county rivals Shrewsbury Town. The 22-year-old - who spent the first half of this season on loan at the Port - was alongside skipper Shane Sutton at the heart of the Bucks defence.
Also coming into the side was Jordan Murphy, whose confidence was lifted with a hat-trick in a 6-0 Shropshire FA Huddersfield Cup semi-final win at Market Drayton Town last week.
Top scorer Marcus Dinanga also bagged a treble in that game but was on the bench, as was fellow forward Kane Richards - signed earlier in the day from Dover Athletic.
Left of the squad were second top scorer Anthony Dwyer, Wolves loanee Connor Johnson and midfielders Jordan Lussey and Henry Cowans.
Southport are managed by Kevin Davies, who was very much a target man in his playing days - most notably for Bolton Wanderers. Therefore, it was not a surprise to see the hosts to start with big Sampson up top.
It was Telford's main striker, Morgan-Smith, who had the first major chance of the game. The ball fell nicely to him in the box, but he dragged it wide of the near post with his left foot.
Jason Gilchrist was another one for the Bucks to look out for as he scored twice against them for FC United of Manchester earlier in the campaign. He had a decent opportunity to get on the scoresheet a quarter of an hour in, but failed to connect with Charles' low cross from close range.
Sampson aimed to use his strength to his advantage. However, it put him at a disadvantage as he was booked for nudging over Telford man Sutton.
Completing the home side's front three was Charles, whose sweet left-footed strike forced Ben Wilson into a smart save just after the half-hour mark.
Osborne was then denied by the fingertips of Wilson. It was one-way traffic - it appeared a matter of when, not if, the Bucks would concede.
As half-time drew near, though, Telford improved. Jon Royle almost netted against his former club - his volley sailing narrowly over the crossbar. He is yet to score this term.
Southport were the better side in the first half - and they went ahead shortly into the second period.
Winning a free-kick 25 yards out, Osborne stepped up to take it and instead of floating the ball over the wall, he whipped it into the far corner - past the outstretched Wilson. Cracking finish.
The Bucks should have equalised on the hour mark. A quick counter-attack saw the ball worked out to Murphy, who found McAtee. Somehow, the 18-year-old Shrewsbury loanee skied it.
He was hauled off just a couple of minutes later, with Richards coming on for his Telford debut. The former Chester player went to left wing.
The Port carried on dominating, though, so Bucks boss Edwards saw fit to make another switch. This time, John Marsden replaced Royle in the middle of park, aiming to add some more bite.
Just after the substitution, though, Southport doubled their lead. Charles - who gave Paul Bignot the run-around all night - cut in from the left-hand side and smacked the ball into the top corner.
Charles soon went from scorer to provider, cutting the ball back for Sampson to finish on the line - to put the game to bed.
Telford made their third change, bringing on Dinanga for Murphy. Mercifully, for the Bucks, and namely Bignot, Charles was taken off as the Port eased to victory in the closing stages, with Morgan-Smith sent for an early shower for a rash challenge.
Edwards' charges have 11 matches left to decide their fate, although they did nothing here to suggest they have enough to survive in this division.
Southport (4-3-3): Worsnop; Richards, Howson, Priestley, Kelly; Lynch (c), C Smith, Osborne; Charles (Dawson, 79), Sampson (Cockerline, 84), Gilchrist
Subs not used: Doyle, Fagan, Halstead (gk)
Telford (4-3-3): Wilson; Bignot, D Smith, Sutton (c), Harris; Deeney, Royle (Marsden, 69), McAtee (Richards, 63); Murphy (Dinanga, 74), Morgan-Smith, Newby
Subs not used: White, Singh (gk)
Referee: James Bell (West Riding)
Attendance: 784 (33 Telford)