The duo made second half appearances for The Eagles but their introduction yielded little as The Blues ran out 3-1 victors at Stamford Bridge.
Spain striker Alvaro Morata opened the scoring for home side Chelsea on 32 minutes before Andros Townsend levelled the score for Palace eight minutes after the interval.
Morata then restored The Blues' lead in the 65th minute, with Pedro Rodriguez sealing the win with a cool effort five minutes later.
In dire need of goals, Palace boss Roy Hodgson threw on striker Ayew a minute after Chelsea's third goal, before midfielder Schlupp joined the action nine minutes later.
Their presence could only prevent Maurizio Sarri's men from finding a fourth goal as The Eagles failed to register any more goals of their own to reduce the deficit.
The result has sent Chelsea second on the league table, with Palace 12 places below.
It was Schlupp's ninth appearance involving six starts this season.
Ayew, on loan from Swansea City, has tallied seven outings involving six first XI berths following a summer transfer.
Both men are still chasing their first season goals, with Ayew having come under high criticism for his goal drought.