Sebastien Squillaci's seventh-minute header gave us the victory but injuries will be of concern with the Carling Cup final and a Champions League match against Barcelona coming up.
Fabregas came off with what appeared to be a knee complaint in the first half while Walcott was carried off on a stretcher with an ankle injury after being flattened by a clumsy Dean Whitehead challenge.
Much of the pre-match talk had been about how we would cope without another of our key men, Robin van Persie, who was ruled out yesterday with a hamstring injury.
Arsene Wenger chose Nicklas Bendtner to lead the attack in his absence while Fabregas, Wojciech Szczesny and Samir Nasri returned after missing Sunday's disappointing draw with Leyton Orient.
Tony Pulis recalled Asmir Begovic and Whitehead while Ryan Shawcross skippered the side almost a year to the day the that he broke Aaron Ramsey's leg at the Britannia Stadium.
Clearly determined to put the shock FA Cup draw behind them, the lads came flying out of the blocks and rattled the Stoke woodwork with barely a minute gone.
Fabregas slotted in Theo Walcott after some good work by Jack Wilshere, and the England winger beat Begovic at the far post but his shot rebounded off the woodwork and into the goalkeeper's hands.
Walcott tore into the Stoke box again three minutes later after being played through by Bendtner but Begovic came out to smother the ball.
The early pressure paid off for the home side when they took the lead.
Bendtner volleyed across the box from a Wilshere corner to find Squillaci, who headed home unmarked from five yards for his first league goal of the season.
Fabregas looked to be struggling with an injury and was replaced by Andrey Arshavin 14 minutes in.
The Spaniard, who missed most of December with a hamstring injury, looked disappointed to have picked up a knock and will be badly missed if he doesn't recover for Sunday's cup final and the Barcelona game in two weeks' time.
We remained in control but played the game at a much slower pace following their captain's departure.
Arshavin, who scored the winner against Barcelona last week, skipped past his marker before drawing a good save from Begovic at his near post.
Szczesny had to scramble down to his right to save John Carew's 25-yard volley with Stoke's first chance of the game at the other end.
The Stoke defence backed off as Arshavin raced at the defence and Shawcross, who had been booed with his every touch, hacked the Russian down 20 yards out.
Nasri curled the resultant free-kick a couple of yards wide of Begovic's goal.
Jonathan Walters entered the book for pulling back Walcott in the closing stages.
The decision angered Pulis, who raged at referee Peter Walton and Wenger, who agreed with the referee's call, in the opposing technical area.
Carew was lucky to escape a booking at the start of the second half when he appeared to push over Johan Djourou after coming in late on the tackle.
The away side almost equalised a minute later when Shawcross' deflected header whistled just past Szczesny's goal.
Earlier this season Wenger accused Stoke of playing like a rugby side because of their dirty tactics and he was angered by a late sliding challenge from Rory Delap on Bacary Sagna which the referee deemed not worthy of a booking.
It was Pulis who was up in arms next though as a result of Gael Clichy's late sliding tackle on Jermaine Pennant, which earned the defender a yellow card.
Stoke were looking much more assured in the second period and they went close when Robert Huth headed just over the bar from a Rory Delap long throw.
We then went on the attack through Arshavin, who dodged a Shawcross sliding tackle to find Walcott in the box but the 21-year-old was off-balance and mis-kicked his attempt on goal.
Walcott was bundled over by Whitehead on the edge of box in the 68th minute but referee Walton waved play on.
The winger stayed on the ground, clearly in pain, clutching his ankle before being carried off to be replaced by Denilson.
Bendtner headed wide from six yards after a Wilshere corner as we looked for a killer second goal with 20 minutes left.
Then Marc Wilson clattered into substitute Marouane Chamakh to earn a booking.
Pennant almost stole an equaliser in the last minute of normal time with a beautiful curling free-kick that went into Szczesny's side-netting.
Wenger was infuriated to see the fourth official show there would be five minutes of injury-time but the lads held the ball for almost the entire added period to ensure a crucial win.