Crystal Palace's Eze earns first call-up as England name squad for Euro 2024 qualifiers
He was the only uncapped player in the 25-man selection for the two games in Group C, away to Malta and at home to North Macedonia.
There was also a call-up for Brighton & Hove Albion defender Lewis Dunk (31) whose one England cap came in 2018 and a recall for Aston Villa defender Tyrone Mings (30).
But there was no place in the squad for Chelsea forward Raheem Sterling (28).
England are top of Group C after winning away in Italy and then at home to Ukraine.
Former Queens Park Rangers player Eze has been in startling form for Palace, scoring six goals in his last eight games and Southgate said he would have been in his previous squad but for an injury setback.
"We have liked him for a long time," Southgate told a press conference. "He has finished the season really strongly and plays in a couple of positions across the attacking line and has a burst of speed to go past people and take people out of the game with his dribbling skills."
Southgate said Dunk and Mings had both earned their calls after strong showing for their clubs, both of whom have finished the season in style with Brighton qualifying for Europe and Villa likely to join them.
Explaining the absence of 82-cap forward Sterling, Southgate said it had been an easy decision.
"I spoke with him a week or so ago. A general catch-up. He is not happy with his condition physically, carrying a hamstring problem. He wasn't really in consideration because he doesn't think he is operating at the level he needs," the coach said.
Southgate also had some words of comfort for Brentford forward Ivan Toney who made his debut as a substitute against Ukraine but has since been banned for eight months after more than 100 breaches of the FA's betting rules.
"When he comes back, if he plays well, then we'll pick him," Southgate said. "I think he'll have additional motivation through what he's experiencing and he's a resilient guy with great character and we are here to support him."
Southgate said he had not considered resting a few of his senior players for what look like two comfortable fixtures. Five Manchester City players in the squad will be playing in the Champions League final days before the Malta game on June 16.
"I don't think the rest of the world will be (resting players) and we've played North Macedonia at home twice and never beaten them," Southgate said.
"I think we could easily fall into the trap - to be a top team, to be European champions we need to nail the fixtures, like we did in March."
Squad: Jordan Pickford, Aaron Ramsdale, Sam Johnstone. Trent Alexander-Arnold, Lewis Dunk, Marc Guehi, Harry Maguire, Tyrone Mings, Luke Shaw, John Stones, Kieran Trippier, Kyle Walker. Jude Bellingham, Eberechi Eze, Conor Gallagher, Jordan Henderson, James Maddison, Kalvin Phillips, Declan Rice. Phil Foden, Jack Grealish, Harry Kane, Marcus Rashford, Bukayo Saka, Callum Wilson.