The Porthcawl-born youngster is the shock inclusion in the Welsh starting XV to face Italy at the Millennium Stadium this Saturday.
Prydie is listed in the Ospreys' academy and first-team squads but he is yet to feature at any stage in the Magners League.
He currently has just seven minutes of first-team action for the Ospreys to his name having become the youngest player in Heineken Cup history during the win over Viadana in December.
And at just at 18 years and 27 days of age, Prydie becomes Wales' youngest ever player beating the record of Norman Biggs set 122 years ago.
He also takes over from England's Matthew Tait as the youngest player to appear in the Six Nations.
Prydie, who is also registered with Principality Premiership outfit Swansea, replaces Leigh Halfpenny of the Cardiff Blues for the visit of the Azzurri.
"Tom has been with us for the duration of the campaign, he was one of two youngsters - brought in alongside Kristian Phillips - who we wanted to have a look at and we've been impressed with him," said Wales coach Warren Gatland, who sprang a major surprise when he first named Prydie in his 35-man training squad back in January.
"We heard some good things about him from his region and from the coaches at under 18 level and he has lived up to that, as has Kristian as well.
"We are not sure if Leigh Halfpenny is going to be able to tour this summer (he may need an operation) and we also need to look at our options for the future and find someone to push the incumbents for the World Cup. There are one or two players out at the Regions who will also be on the radar but this is a great opportunity for Tom.
"He is the fastest player in the squad, he can play at full back as well as on the wing and he is not afraid to tackle so we'll see how he goes."
Prydie is one of five changes to the side that lost 27-12 to Ireland last weekend, with fellow youngster Sam Warburton another headline grabber after being given the nod ahead of Blues veteran Martyn Williams on the openside flank.
Ospreys skipper Ryan Jones returns to captain the side having missed the trip to Dublin with a calf strain, while British & Irish Lions tourists Gethin Jenkins and Mike Phillips are both included in the starting line up having recovered from injury.
"We have an eye on the future as well with the selection of Sam Warburton in the back row, but both players come into the side alongside players who will also add experience and leadership," added Gatland.
"Ryan returns to lead us as captain, Gethin joins the front row and re-forms the all Lions front row for the first time since that tour, and Mike adds his considerable experience and talents to the backs.
"At scrum half we are conscious that we need three players to all be pushing each other for a starting place and we have been happy with what we have seen from Richie Rees this tournament. Dwayne (Peel) is being given another chance; we want him to make an impact from the bench and improve on his showing last time out.
"We are under no illusion that Italy will be a tough prospect on Saturday. We found it hard to break them down here two years ago and they have performed well in each game of the tournament so far and with a good win over Scotland under their belts we will be a target for them.
"We are all very disappointed and we need to demonstrate our passion and pride in the Welsh jersey on Saturday and show everyone what it means to us to play for our country."
Wales
15 Lee Byrne (Ospreys)
14Tom Prydie (Ospreys)
13 James Hook (Ospreys)
12 Jamie Roberts (Blues)
11 Shane Williams (Ospreys)
10 Stephen Jones (Scarlets)
9 Mike Phillips (Ospreys)
1 Gethin Jenkins (Blues)
2 Matthew Rees (Scarlets)
3 Adam Jones (Ospreys)
4 Bradley Davies (Blues)
5 Luke Charteris (Dragons)
6 Jonathan Thomas (Ospreys)
7 Sam Warburton (Blues)
8 Ryan Jones (Ospreys, captain)
Replacements
16 Huw Bennett (Ospreys)
17 Paul James (Ospreys)
18 Ian Gough (Ospreys)
19 Gareth Delve (Gloucester)
20 Dwayne Peel (Sale Sharks)
21 Andrew Bishop (Ospreys)
22 Tom Shanklin (Blues)
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