Both teams have already qualified for the last 16 but the result at Wembley will determine who finishes top of Group D.
There was a clamour for Southgate to make attacking changes after a flat performance in last week's 0-0 draw against Scotland and he will hope the introduction of Grealish and Saka will inject some creativity.
Captain Harry Kane leads the line despite heavy criticism over his lacklustre performances so far while Mason Mount and Ben Chilwell are not in the squad because they are self-isolating due to coronavirus protocols.
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