The Ospreys wing is joined by returning British & Irish Lions Ryan Jones, who is re-instated as captain, Gethin Jenkins and Mike Phillips.
Prydie replaces Blues wing Leigh Halfpenny, who misses out altogether, Jenkins replaces Osprey Paul James, who is on bench duty, allowing Wales to field their all-Lions front row which will be together for the first time since the 2009 Test series against South Africa.
Ospreys No 9 Phillips also makes his first Wales start since featuring for the Lions against the Springboks, taking over from Richie Rees, with Dwayne Peel keeping his place on the bench to provide the scrum half cover. Warburton is selected in place of his regional colleague Martyn Williams in the back row which also sees Jones replace Gloucester's Gareth Delve, who moves to the bench.
"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.
"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 will be Wales' 1,074th cap, and takes over the 'youngest Welsh international' mantle from fellow wing Norman Biggs who was capped as a Cardiff player in 1888 at 18 years and 50 days. The previous youngest player in the 6 Nations before this was Matthew Tait (England) two days before his 19th birthday.
"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," continued 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 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: Lee Byrne; Tom Prydie, James Hook, Jamie Roberts, Shane Williams; Stephen Jones, Mike Phillips; Gethin Jenkins, Matthew Rees, Adam Jones, Bradley Davies, Luke Charteris, Jonathan Thomas, Sam Warburton, Ryan Jones (captain)
Replacements: Huw Bennett, Paul James, Ian Gough, Gareth Delve, Dwayne Peel, Andrew Bishop, Tom Shanklin
15 Lee BYRNE (OSPREYS - Cap No 1,041)
DoB: 01.06.80. 6'3" / 1.91m. 15st 1lb / 96kgs
International record: 31 caps (W 13, L 17, D 1; 40 pts - 8T)
14 Tom PRYDIE (OSPREYS)
DoB: 23.02.92. 6'4" / 1.94m. 13st 10lbs / 87kgs
International record: Uncapped
13 James HOOK (OSPREYS - Cap No 1,047)
DoB: 27.06.85. 6'0" / 1.83m. 14st 10lbs / 93kgs
International record: 41 caps (W 17, L 23, D 1; 214 pts - 7T,34C,35PG,2DG)
12 Jamie ROBERTS (CARDIFF BLUES - Cap No 1,057)
DoB: 08.11.86. 6'4" / 1.93m. 16st 10lbs / 107kgs
International record: 20 caps (W 9, L 11; 5 pts - 1T)
11 Shane WILLIAMS (OSPREYS - Cap No 976)
DoB: 26.02.77. 5'7" / 1.71m. 12st 11lbs / 81kgs
International record: 72 caps (W 34, L 36, D 2; 250 pts - 50T)
10 Stephen JONES (SCARLETS - Cap No 966)
DoB: 08.12.77. 6'1" / 1.86m. 15st 0lbs / 95kgs
International record: 87 caps (W38, L47, D2; 776 pts - 7T,126C,158PG,5DG)
9 Michael PHILLIPS (OSPREYS - Cap No 1,022)
DoB: 29.08.82. 6'3" / 1.91m. 16st 4lbs / 103kgs
International record: 38 caps (W 20, L 17, D 1; 20 pts - 4T)
1 Gethin JENKINS (CARDIFF BLUES - Cap No 1,006)
DoB: 17.11.80. 6'2" / 1.88m. 19st 4lbs / 122kgs
International record: 73 caps (W 32, L 39, D 2; 15 pts - 3T)
2 Matthew REES (SCARLETS - Cap No 1,033)
DoB: 09.12.80. 6'0" / 1.83m. 17st 3lbs / 109kgs
International record: 35 caps (W 16, L 18, D 1; 10 pts - 2T)
3 Adam JONES (OSPREYS - Cap No 1,018)
DoB: 08.03.81. 6'0" / 1.83m. 19st 10lb / 125kgs
International record: 60 caps (W 30, L 28, D 2; 10 pts - 2T)
4 Bradley DAVIES (CARDIFF BLUES - Cap No 1,065)
DoB: 09.01.87. 6'6" / 1.98m. 18st 11lbs / 119kgs
International record: 9 caps (W 5, L 4)
5 Luke CHARTERIS (NEWPORT GWENT DRAGONS - Cap No 1,030)
DoB: 09.03.83. 6'9" / 2.06m. 10st 5lbs / 129kgs
International record: 21 caps (W 10, L 11)
6 Jonathan THOMAS (OSPREYS - Cap No 1,013)
DoB: 27.12.82. 6'5" / 1.96m. 17st 13lbs / 114kgs
International record: 54 caps (W 26, L 26, D 2; 35 pts - 7T)
7 Sam WARBURTON (CARDIFF BLUES - Cap No 1,070)
DoB: 05.10.88. 1.88m / 6'2". 15st 11lbs / 100kgs
International record: 5 caps (W 3, L 2)
8 Ryan JONES (OSPREYS, CAPTAIN - Cap No 1,029)
DoB: 13.03.81. 6'5" / 1.96m. 18st 0lbs / 114kgs
International record: 39 caps (W 22, L 16, D 1; 5 pts - 1T)
16 Huw BENNETT (OSPREYS - Cap No 1,017)
DoB: 11.06.83. 6'0" / 1.83m. 16st 10lbs / 106kgs
International record: 31 caps (W 17, L 14)
17 Paul JAMES (OSPREYS - Cap No 1,021)
DoB: 13.05.82. 6'1" / 1.86m. 18st 4lbs / 116kgs
International record: 9 caps (W 4, L 5)
18 Ian GOUGH (OSPREYS - Cap No 964)
DoB: 10.11.76. 6' 6" / 1.98m. 18st 11lbs / 119kgs
International record: 62 caps (W 29, L 30, D 3; 5 pts - 1T)
19 Gareth DELVE (GLOUCESTER RUGBY - Cap No 1,043)
DoB: 30.12.82. 6'3" / 1.91m. 17st 13lbs / 114kgs
International record: 10 caps (W 4, L 6; 5 pts - 1T)
20 Dwayne PEEL (SALE SHARKS - Cap No 994)
DoB: 31.08.81. 5'9" / 1.76m. 13st 8lbs / 86kgs
International record: 73 caps (W 34, L 37, D 2; 25 pts - 5T)
21 Andrew BISHOP (OSPREYS - Cap No 1,059)
DoB: 07.08.85. 6'0" / 1.83m. 14st 12lbs / 94kgs
International record: 9 caps (W 6, L 3)
22 Tom SHANKLIN (CARDIFF BLUES - Cap No 993)
DoB: 24.11.79. 6'2" / 1.88m. 15st 9lbs / 99kgs
International record: 65 caps (W 31, L 33, D 1; 100 pts - 20T)