Leicester striker Vardy and Chelsea defender Cahill have both been regulars in Southgate’s squads since he was appointed in November 2016.
While neither have completely “shut the door” and would be willing to play under exceptional circumstances, it is likely that both made their final international appearances at the 2018 World Cup.
“This has been on my mind for a while,” Vardy, who has made 26 England appearances, told the Guardian.
“I’m not getting any younger and you can see, to be fair to the gaffer, he wants to make it more youthful, which obviously had its benefits during the World Cup – we got to the semi-finals and finished fourth, which is equal to the furthest we have ever been on foreign soil.
“So I just said to Gareth that I think it’s probably best from now on, especially with the way he wants to go, to bring youngsters in who he thinks have got the ability and start nurturing them into international football.”
Having made his international debut in 2010, Cahill has amassed 61 appearances for his country.
With an emphasis on youth in the England setup, the 32-year-old Cahill is ready to step aside.
“I think in terms of my international future I think it’s time I take a step back now. I feel that it’s the right moment to do that,” Cahill told Chelsea TV.
“I have been hugely proud of what I have achieved in terms of over 60 caps, I’ve captained my country on a few occasions which has been a huge honour, it’s something I have been really proud of in terms of my career.
“I can see now it’s going in a younger generation and I think for me to take a step back now is the perfect time.”
Vardy initially shared his thoughts with Southgate at the start of the Premier League season and was given time to mull over his decision, according to Sky Sources.
However, the period of reflection has not altered his view, and it appears his England career will end with seven goals.
Much like James Milner, Vardy and Cahill have told Southgate they would be prepared to return in exceptional circumstances, such as an injury crisis.
Both decisions had been anticipated by Southgate, who is expected to recall Liverpool’s Joe Gomez when he announces his latest squad on Thursday. It remains to be seen who will take Vardy’s place up front.
Southgate is picking players for England’s Nations League opener against Spain on September 8, live on Sky Sports, and a friendly with Switzerland three days later.