The eighth-seeded Tigers, who dropped to 11-8 with the loss, will now compete in the Class L state tournament.
Darien (19-0) won the match by scores of 25-19, 25-16 and 25-9.
Darien ripped Ridgefield 3-0 in the FCIAC quarterfinals at home on Tuesday.
Jessica Roth had 17 assists, 12 service points and nine digs for the Tigers.
Olivia Prehodka added five kills, nine service points and 16 digs, and Lauren Liederbach had six kills, five service points and eight digs.
Riley Sousa (nine), Kelly Kosnik (seven) and Claire Naughton (six) combined for 22 kills for Darien. Kathleen Burke had 26 assists.