Paul Merson opened the scoring on the half hour mark when he took advantage of good approach play down the left and when the ball was played into the box he sidefooted past Vince Bartram.
Former Celtic striker Mark Burchill eventually made it two, finding it third chance the charm when he slotted in the second on the stroke of half-time.
The second half saw Pompey play in neutral and the home side took advantage of this when substitute Kevin James headed back across Shaka Hislop and into the net in the 68th minute.
However, Gary O'Neil restored the two goal advantage and Pompey have created a three point gap at the top of the table.
Norwich missed the opportunity to keep apace with Portsmouth in a fiery encounter at Carrow Road.
The Blades went two up inside seven minutes with goals from Michael Brown and Michael Tonge. Norwich boss Nigel Worthington was sent off but then saw his club fall further behind when Carl Asaba stroked home a 40th minute penalty.
With the referee threatening to lose control of the situation, a couple of meaty challenges eventually saw Iffy Onoura sent off, four minutes from the break.
Despite the man advantage, it took until the final moments for Norwich make much headway in the second half. Paul McVeigh stabbed home from close range and Malky Mackay added a second just before the final whistle but the two late goals were not enough to avoid defeat.
Jordan Stewart's 81st minute strike ensured Leicester emerged from Selhurst Park with a victory in a five-goal thriller, a game in which they were two goals behind.
Mark Williams's first goal in over a year and Neil Shipperley's excellent curling free-kick put Wimbledon two goals to the good inside a quarter of an hour.
The Foxes fought back and Trevor Benjamin was credited with a scrappy looking 43rd minute goal and Muzzy Izzet equalised from the spot in injury time. Both sides had chances to win it but Stewart it was who turned his man before hitting an impressive drive past Kelvin Davis with nine minutes remaining to send Leicester second.
It was a game of two halves at Pride Park when Derby dominated the first 45 minutes but the introduction of Glen Little totally changed matters as Burnley ran out 2-1 winners.
Adam Bolder gave the home side the lead after just eight minutes but John Gregory's side were made to pay for missing a succession of chances by a plucky Burnley team.
Two goals in five minutes through a Robbie Blake penalty and a Warren Barton own goal gave The Clarets an impressive three points and move them off the bottom of the table, with Grimsby replacing them.
Darren Ward's towering header in the 73rd minute gave Millwall a 1-0 win over Brighton. The visitors' cause was not helped when Robbie Pethick was ordered off just after The Seagulls conceded for an off-the-ball incident.
In the two early games, Watford eventually broke down a resolute Walsall defence and emerged from the game with a 2-0 victory.
Tommy Smith got the first as substitute Anthony McNamee's cross eluded the defence and left the striker with the simple task of beating keeper James Walker from close range.
The visitors had Danny Sonner sent off for a late foul five minutes from time and The Hornets capitalised by doubling their advantage in the last minute.
A long punt upfield left Smith in space and he turned and hit a great reverse pass to Dominic Foley, who was able to run in unmolested and smashed the second home.
In the other 1pm kick-off, Rotherham and Reading could not find a way through the opposing defence and the game ended 0-0.
Click below for more information on the games:
English Division One:
Derby County v Burnley
Gillingham v Portsmouth
Millwall v Brighton & Hove Albion
Norwich City v Sheffield United
Rotherham United v Reading
Watford v Walsall
Wimbledon v Leicester City
Click here for the Division One table
