The Bombers kicked seven of the last eight goals – including two to nil in the fourth term - to reel-in the Eagles' 23-point half-time lead and get their finals aspirations back on track.
The heart-breaking defeat was the Eagles' third loss from a strong position in Melbourne this season, and dealt a savage blow to their finals hopes.
West Coast remains anchored to 11th spot on the ladder and could be two games outside the eight after round 21 is complete.
Simpson was despondent in his post-game press conference after watching his team grind to a halt in the face of the Bombers' onslaught at Etihad Stadium.
"It was like watching a trainwreck in slow motion in that last quarter," he said.
"When you get that much time I suppose you think you can do some moves or influence the trend.
"I thought (Dyson) Heppell (38 possessions) going back, we didn't handle that. The players didn't handle that.
"They did a few different things in the second half. Our defenders fought really hard today, they were exceptional, but we just didn't have enough run in that last quarter.
"Losing (Sam) Butler didn't help. A six-day break, all that sort of stuff but the game was there for us.
"The boys and the coaches are very disappointed."
The Eagles' run seemed to evaporate as they reverted to kicking long to their tall targets in the second half.
"We wanted to be brave with the ball, but you've got to work for it. It's probably not the kickers' fault, it's more the work off the ball,"Simpson said.
"So when we got tired that work rate dropped and Essendon, to their credit, worked harder."
West Coast rehashed nightmares from their loss to Carlton from four goals up in the final term in round six, and from 18 points ahead during the third quarter against Collingwood in round 10.
"We're just not tough enough for long enough," was Simpson's explanation.
"I think every team probably has one or two opportunities in the season where they miss that opportunity.
"It's not something you want to go through three times though."
Simpson said he was unsure about the extent of Butler's eye injury, which forced him from the field in the third quarter. The defender was subbed out in the final term.
"(It's) not great, that didn't help the situation either. I haven't got the full medical update, but it was bad enough to get subbed," Simpson said.
"I think he either had a cut on the eye or bleeding behind it."
Twitter: @TravKing_AFL