Experienced duo Dixon and Fairbrother hit the milestone as Head Coach Bernard Jackman makes eight changes for the big Round 3 European encounter.
Dixon returns in the centre where he joins forces with Adam Warren who also earns a starting jersey.
Wings Dafydd Howells and Zane Kirchner will provide the firepower out wide, with Hallam Amos moving to full back.
A new-look half back pairing will see scrum half Tavis Knoyle and fly half Josh Lewis combine. Fly half Arwel Robson unfortunately misses the game as a pre-caution after a tight hamstring in final preparations.
Two changes in the pack see a return for Samoa international lock Brandon Nansen and back row Nic Cudd.
The replacements bench features call-ups for Rhys Lawrence, Nicky Thomas, Matthew Screech, Huw Taylor, James Benjamin, Rhodri Davies and Josh Lewis.
Jackman said: “It will be an incredible tough game as Northampton Saints have lots of quality.
“However, we want to bounce back from last week’s disappointing display and it’s an opportunity to show the character in the squad.
“It’s a very special day for both Lloyd (Fairbrother) and Jack (Dixon) who are both integral parts of the squad,” he added.
“It’s a great milestone to reach 100 games for your region. Both are still young men who are highly respected by their peers and who will be determined to put in a big performance on the day.”
Dragons: Hallam Amos, Dafydd Howells, Adam Warren, Jack Dixon, Zane Kirchner, Josh Lewis, Tavis Knoyle; Ryan Bevington, Richard Hibbard (c), Lloyd Fairbrother, Brandon Nansen, Lewis Evans, Harrison Keddie, Nic Cudd, Ollie Griffiths
Replacements: Rhys Lawrence, Aaron Jarvis, Nicky Thomas, Matthew Screech, Huw Taylor, James Benjamin, Rhodri Davies, Jordan Williams
Northampton: George Burbank, Ollie Sleightholme, Rory Hutchinson, Luther Burrell, Taquele Naiyaravoro, Dan Biggar, Alex Mitchell; Alex Waller (c), James Fish, Ben Franks, Api Ratuniyarawa, Alex Moon, Jamie Gibson, Tom Wood, Teimana Harrison
Replacements: Reece Marshall, Will Davis, Ehren Painter, David Ribbans, Mitch Eadie, Cobus Reinach, Fraser Strachan, Andrew Kellaway
