The first-team duo have started Under-21 fixtures this month but, until now, neither had completed a game since recovering from the long-term injuries that hampered them last season.
Wilshere operated in an advanced midfield role while Sagna played the first half at right-back before moving into a central role after the break.
The visitors won the game courtesy of well-taken goals from Billy Clifford and Islam Feruz.
Chelsea captain John Terry was also involved for the first 45 minutes having announced his international retirement last month while Andre Santos, Francis Coquelin, Andrey Arshavin and Marouane Chamakh and Emmanuel Frimpong all figured for the Gunners.
Wilshere, fully recovered from the knee injury which kept him out for 12 months, went close to an equaliser in the 65th minute at London Colney, surging into the box and forcing a low save from Jamal Blackman.
Encouragingly for Arsenal, Wilshere and Frimpong showed little sign of lack of match practice, both making driving runs into Chelsea territory late on in the friendly.
And Sagna also looks to be nearing manager Arsene Wenger's plans after overcoming the second leg break he suffered in the 2011/12 season.
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Support the USA national team with an official 2013 Centennial soccer jersey from Nike. Its Official.
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