James Justin and Jarrod Bowen were called up for Nations League games
Bowen has scored 18 goals and provided 13 assists for the Hammers this season.
The 25-year-old was in contention for the previous England squad in March but was ruled out by a fractured foot bone.
Leicester City right-back James Justin is named for the first time, and Fikayo Tomori is recalled for June's matches after helping AC Milan win Serie A.
Leeds United midfielder Kalvin Phillips and Newcastle United defender Kieran Trippier also return after injury.
Liverpool captain Jordan Henderson is not named among the midfielders after a heavy workload in a season that will only end on Saturday in the Champions League final, with Southgate saying, "I don't need to know any more about him".
The England boss suggested that was also his reason for leaving out Tottenham Hotspur defender Eric Dier, saying the 28-year-old was "definitely in our thinking".
There is no place for Henderson's Liverpool team-mate Joe Gomez, so Trent Alexander-Arnold He is the only representative of a Reds squad looking to complete a treble of cups this season when they face Real Madrid in Paris.
As Southgate indicated it would be the case, Manchester City's Kyle Walker returns to the squad despite not having played in the Premier League since mid-April because of an ankle problem.
Southgate said he had selected 11 defenders in his squad because of doubts over the fitness of some.
"It is a bit of a minefield in terms of players who have missed football and are coming back from injuries," he said. "Luke Shaw and Ben Chilwell haven't played at all. Marc Guehi is a doubt.
"Fikayo has had a perfect season with AC Milan, and I talked in March about wanting to look at some of the young centre-backs coming through, and some of these guys are slightly ahead of Tyrone [Mings], who has always played well for us.
"At the same time, we have to make opportunities for good young players to have a look at them."
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