The Dutchman is yet to appear for the Magpies at St James' Park since joining the club over four years ago, but will be given his chance by caretaker boss Chris Hughton against the Terriers.
Krul came off the bench to make some fine saves on the opening day of the season against West Brom and will replace Steve Harper against the League One side.
Midfielder Joey Barton (foot) and striker Andy Carroll (groin) missed the victory at Crystal Palace on Saturday and will remain sidelined.
Slovenian attacking midfielder Haris Vuckic, 17, is included in the first-team squad for the first time since joining the club in January.
TIM KRUL'S DEBUT FOR NEWCASTLE -
NOVEMBER 2nd 2006 PALERMO 0 NEWCASTLE UTD 1
Newcastle claimed a fine 1-0 win in Palermo to move to within touching distance of a place in the third round of the UEFA Cup.
Albert Luque's 37th-minute header capped an impressive first half from the Magpies.
As Palermo pushed for an equaliser in the second half, debutant goalkeeper Tim Krul kept Glenn Roeder's side in the game with several match-winning saves.
Palermo simply could not find a way past the Dutch giant and the handful of Newcastle fans were able to celebrate with calls of 'we are top of the league' at the final whistle.
Luque earned a rare start in attack with Glenn Roeder having little option but to thrust the Spanish striker in to the fray due to injuries and the unavailability of Giuseppe Rossi.
Roeder had said it was up to Luque to prove he deserved a regular place in his side - however it was James Milner who looked the more motivated.
Shifting from the left-wing into a support role up front, the 20-year-old created the biggest threat for the Magpies.
Having first tested Alberto Fontana from just inside the area, his trickery allowed him to turn Andrea Barzagli inside the six-yard to make room for another shot, but he appeared to be impeded unfairly by the Palermo defender.
His shot was too weak to test Fontana while his stronger claims for a penalty fell on deaf ears.
Palermo had shown the more going forward inside the opening 10 minutes and Craig Moore twice came to the rescue of Krul with last-ditch clearances.
Krul, the second youngest player to ever play in Europe for Newcastle, looked a little nervous and his kicking was particularly wayward with the home side's brightest player Franco Brienza almost capitalising on a poor clearance, only to fire over from 25 yards.
As the visitors began to push forwards again, Milner provided the opportunity for Luque to open his account for the season, and he did not disappoint either.
With Barzagli and Hernan Dellafiore both stood like statues in the middle, Luque stole in between the pair to head in Milner's left-wing cross and give Newcastle a lead they perhaps merited on the balance of play.
The goal was only the second Palermo had conceded at the Renzo Barbera in seven European games, the first since September 9 last year.
And the scorer back then will be familiar to Newcastle fans - Georgian midfielder Temuri Ketsbaia who netted for Anorthosis Famagusta in a 2-1 defeat.
Palermo were keen not to lose their unbeaten home European record, though, and camped in the Newcastle half for the second half.
It was backs-to-the-wall stuff for Roeder's men, but just as the Newcastle manager had predicted on Wednesday, it was time for one of his youngsters to make a name for himself.
After a good hour's play, Krul had certainly settled down and began to repay Roeder's faith with a string of good saves.
Palermo substitutes Giuseppe Biava and David Di Michele both failed to beat him as Brienza's left-wing free-kick seemed certain to produce the equaliser.
First, Krul dived low to tip Biava's stooping header to his left and then he got back onto his feet to block Di Michele's follow-up.
The Dutch shot-stopper then produced another top-drawer save to deny Andrea Carracciolo as Palermo increased the pressure.
But several wayward passes convinced the home fans it was not going to be their night and Newcastle were comfortably able to play out time.