The 34-year-old's performances at Sunderland have belied his advancing years and led to a surprising international turnaround, having won the last of his 55 international appearances in November 2013.
Sunday's World Cup qualifier against Lithuania saw him win his long-awaited 56th cap, being deployed from the start at Wembley as England looked to prise open the visitors' well-drilled, packed defence.
The decision paid dividends as Defoe swept home Raheem Sterling's cross midway through the first half to set England on course for a straightforward 2-0 win.
"It's a great moment for him," Southgate said of England's man of the match after his 20th international goal.
"He was thrilled to be back involved in the squad, I think he has enjoyed his week immensely.
"He's been a good senior professional to have around the team, both in terms of the way he's trained, his professionalism, which has been great for some of the younger players to see, and his finishing in training and then today, which we expected really.
"I would have put my house on him scoring at some stage today, so I think he's had a really positive impact on everybody."
Defoe struggled to keep his emotions in check as he wound back the years at Wembley, where he led the team out with Bradley Lowery, the terminally-ill five-year-old who calls the Sunderland striker his "best mate".
It was a special day for a striker who has established himself in Southgate's thinking in the absence of Wayne Rooney, Harry Kane and Daniel Sturridge.
Defoe, so devastated to be overlooked for the World Cup in Brazil three years ago, could even head to Russia next summer at the age of 35.
"I think we've got to look every time we get together as to who is in form," Southgate said when asked if the striker was a realistic proposition for the 2018 World Cup.
"I don't know if we can have a distinct pecking order because players that are playing well deserve the opportunity.
"If we are going to be successful, we have got to have that competition for places.
Read the full article on eurosport.co.uk: 'I would have put my house on Defoe scoring', says England boss Southgate