Midfielder Michael Simmonds struck two minutes into his debut as Horsham YMCA beat Eastbourne United 4-0 at Gorings Mead.
Simmonds, promoted from the reserves, finished after Paul Boxall had headed on a fine Duffield cross.
Boxall later forced home Ellis Hooper's header before Andy Lynch wasted a golden chance for United.
That proved the turning point. Matt Duffield made it three by half-time and Joel O'Hara rounded things off with a clinical finish.
In the John O'Hara Cup third round, champions Sidley United saw off Selsey 3-2 with Owen Ball getting a brace and defender Mark Ralley also popping up with a goal.
Selsey's goals came from Paul Lee and Tom Ford.
Sidley joint-boss Peter Heritage said: "We won this cup last season and we want to win it again. We thoroughly deserved the win though our keeper Danny Poole made a fantastic save at 2-1."
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