Youngs replaces scrum-half Mike Phillips, Bowe forces right wing Alex Cuthbert onto the bench and Lydiate is preferred ahead of blindside flanker Tom Croft, who must also settle for a place among the replacements.
Completing the new arrivals are loosehead prop Mako Vunipola and lock Geoff Parling, who have profited from injuries to Alex Corbisiero and Paul O'Connell.
Ryan Grant, Sean O'Brien and Conor Murray have been included on the bench after missing last weekend's 23-21 victory over Australia altogether.
Probably the biggest call of the five changes was Phillips' omission with head coach Warren Gatland confirming that he could have played, despite being troubled by a knee injury.
The Wales scrum-half was outclassed by Australia's Will Genia in the first Test, but the omission of a veteran from the 2009 tour to South Africa as the Lions seek to secure their first series triumph for 16 years will have surprised many.
"Mike was fit and available. He's had problems with a sore knee so he hasn't been able to take a full part in training. The decision was to rest him," Gatland said.
"He's potentially an important component of next weekend. All of the nines have done a great job and we felt it prudent to make sure he was 100% for next week by giving him a few days off his feet."
Cuthbert - the scorer of a fine try at the Suncorp Stadium - is unfortunate to lose out, but the firepower offered by Bowe meant his return was inevitable once the Ireland wing was passed fit.
Bowe, who started all three Tests in South Africa in 2009, broke his hand three weeks ago but has made an astonishing recovery after undergoing surgery to repair the damage.
The 29-year-old will wear a hurling glove for protection and revealed that he faced intensive physiotherapy to put himself in contention for Saturday.
"To have fractured my hand and still be here and now go into one of the biggest matches of my career feels pretty surreal," Bowe said,
"I feel fully primed and ready to go. I've been having physio three to four times a day and have been consistently icing my hand. It's been a pretty frantic regime but it's amazing how good my hand feels.
"I know I am capable of getting myself back up to match speed pretty quickly."
Croft could also argue a case for his continued involvement in the starting XV on the basis of his display in Brisbane, but Gatland places enormous value in the tackling of Lydiate.
"This is a do or die match for Australia. It's going to be a real battle out there so we've decided to add a little more physicality to our side up front and Dan brings that," Gatland said.
"We also have the explosiveness coming off the bench that Tom Croft and Sean O'Brien give us. We're really happy with the quality on the bench.
"The five changes show how strong the squad is and that we have a huge amount of competition in the team.
"It's not about changing a winning side, it's about picking the best team to do a job for us. We can win this series by winning on Saturday.
"The last thing we want to do is have the series balanced at 1-1 with another match to play in Sydney. Everything is about Saturday night."
Vunipola and Parling were the natural replacements for Corbisiero and O'Connell once they had been struck by a calf problem and fractured arm respectively.
O'Connell will miss the rest of the series, but is staying with the squad in Australia.