The 17-year-old academy graduate has shone for Saints since breaking into the first team, leading to links with the likes of Chelsea and Arsenal.
Shaw's form has twice been rewarded with call-ups by the Young Lions but on both occasions he has had to pull out of the squad.
Despite that, Stuart Pearce on Tuesday named him in his 23-man squad for Israel and the left-back, joined in the squad by team-mate Nathaniel Clyne, is keen to make his mark.
"It is very good to be picked for England's Under-21 team, especially with Clyney," Shaw told Saints Player. "Hopefully this time I don't get ill or injured so I don't miss out on this one.
"I've been very unlucky with England. The first time I got called up, I went there and got injured in the training session. Hopefully this time I can stay fit and well.
"With Danny Rose suspended for the first game, hopefully I can show what I can do in training and start.
"This is probably the biggest honour for me. I have played for my country at Under-17s level and I have always wanted to push on.
"Hopefully this can be chance to show England coaches what I can do."
Shaw and Wigan's Callum McManaman are the only two uncapped Under-21s players in what is an experienced 23-strong squad.
Saints right-back Clyne has promised to take friend and team-mate Shaw under his wing and believes England can enjoy a successful summer.
"I am sure I will be rooming with him, looking after him and he will follow me," Clyne said.
"He has not had an appearance yet but he is good enough, otherwise he would not have been called up.
"It gives us an experience and a chance to show everyone what we are capable of. Hopefully we can do well and make the fans proud, as well as our friends and family.
"We played our last nine games, we have won every single one and not conceded. That shows we are good defensively and we score a lot of goals as well.
"If we take our friendly form and international form into the tournament, we could do well."