Both were hurt during the third quarter at the MCG on Saturday with the game already out of reach, as the Dockers copped a 46-point hammering that all but ended their fading finals hopes.
Darcy (ankle) finished the match on crutches and Walker had to be taken from the field on a stretcher after hurting his right knee in an awkward landing.
The 20-year-old defender looked to be in extreme pain as teammates and medical staff rushed to his side.
"He's done something pretty serious," Dockers coach Justin Longmuir said.
"He's going to miss a fair bit of footy, I'd imagine."
Darcy and Walker are both set to have scans on Sunday when they return to Perth.
Fremantle took to the field in front of 61,157 fans - the largest home-and-away crowd in club history - and were torn apart by a slick home side that revelled in the bulk of the support.
Collingwood dominated the contest in the second quarter and piled on 10.1 to 2.1 for the term, putting the result beyond doubt by half-time.
Longmuir hopes his young midfielders - including Neil Erasmus, Matt Johnson, Nathan O'Driscoll and Liam Henry - will grow from the experience.
"The energy and speed which they played with around the midfield in that second quarter was top shelf, and we want to get to that level," Longmuir said.
"(Our players) all got a look at an elite midfield today, so we need to take lessons from that."
Fremantle (7-10) reached the second week of the finals last season but will need a dramatic turnaround to get back there this year, having lost five of their last six games.
"It's disappointing but we've still got a lot we can get out of the season," Longmuir said.
"We need to make sure that we're playing footy in the right way, that we're learning from all these experiences and we build on what we're doing at the moment."
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