The trio are all handed first-ever senior outings for Blues in a team captained by Ellis Jenkins that contains a mix of youth and experience.
A total of 16 players out of the match day squad are products of the Academy at Blues with centre Smith paired alongside Lucas Amorosino in midfield – the Argentine the sole survivor from the side that faced Munster last weekend.
Wales international Scott Andrews packs down with Rhys Williams and Tom Davies up front while lock Loud Reed joins forces with Chris Dicomidis at second row.
Jenkins skippers the side from openside flanker with newcomer Groves and Rory Watts-Jones joining him in the back row.
Wing Davies provides the firepower out wide, with Tom Williams and Dan Fish completing the back three. The half back pairing is Simon Humberstone and Tavis Knoyle.
The bench contains a number of potential debuts with Ethan Lewis, Callum Lewis, Dillon Lewis, Ben Roach, Will Thomas and Jack Phillips all in line for a first team bow if they come on in the north east of England.
Coach Andi Kyriacou, who himself enjoyed a playing stint in England with Saracens, said: “Like any English Premiership side, they are always physical up front and, from watching the footage, they have got strike power in the back line too. They also have a good tactical kicking game.
“I have been up to Newcastle many times as a player and it’s a very tough place to go. We have got to prepare mentally for the challenge ahead.
“Reading in the media, they look like they are going to go pretty loaded with their team selection. They see it as a prequel for their next Premiership game so it’s a good challenge for us and we will rise to it.”
Cardiff Blues: 15 Dan Fish, 14 Tom Williams, 13 Lucas Amorosino, 12 Garyn Smith, 11 Harry Davies, 10 Simon Humberstone, 9 Tavis Knoyle; 1Thomas Davies, 2Rhys Williams, 3 Scott Andrews, 4 Lou Reed, 5 Chris Dicomidis, 6 Jevon Groves, 7 Ellis Jenkins (c), 8 Rory Watts-Jones
Replacements: 16 Ethan Lewis, 17 Callum Lewis, 18 Dillon Lewis, 19 Miles Normandale, 20 Ben Roach, 21 Tomos Williams, 22 Will Thomas, 23 Jack Phillips