After losing co-captain Bonnie Toogood last week to a long-term knee injury, the Bombers rebounded superbly on Saturday in Perth and won 6.5 (41) to 3.7 (25) for their first win of the season.
Prespakis was outstanding throughout, racking up 27 disposals in a best-afield game.
Fellow onballer Georgia Nanscawen also was prominent in the win, with 25 possessions and six clearances.
It is the first loss for the Eagles' high-profile coach Daisy Pearce, and her review will focus heavily on their disastrous opening term, when they somehow managed no inside-50s despite good conditions.
Prespakis had ice on her right quad after the match.
"No injury concern - I carried a bit of a contusion in my quad this week, so a bit of blood on the muscle, (and) it just restricted the movement a little bit," she told Fox Footy
"I fought through it really well today and there was no way I was missing out (on the win)."
The Bombers started as outsiders after losing Toogood among four changes, following last week's loss to Fremantle, while the Eagles were coming off a first-up win.
"We came together as a good group - that's what good teams do," Prespakis told Fox Footy.
"We had some young girls stand up today - it was a good win.
With Prespakis and Nanscawen dominant in the midfield, Essendon swamped West Coast in the first term.
The Bombers had 14 inside-50s to none, outworking the Eagles, with Emily Gough and debutant Chloe Adams putting Essendon on the board.
They should have been three goals up, with a Prespakis shot after the siren also going through.
But the umpires controversially ruled she had run off her line in taking the kick and the goal was disallowed. The replay strongly suggested it was a fierce call on the Bombers star.
"I don't reckon I did (go off the line) ... I thought it was a goal," Prespakis said post-game.
While Jacqui Vogt soccered through Essendon's third goal early in the second, West Coast were lifting.
A great contest from Ella Roberts set up Isabella Lewis for the home side's first goal at 12 minutes.
Mikayla Western goaled on the run shortly before half-time to keep the Eagles in the game, only two goals down despite the Bombers' strong start.
As Essendon gave away three inside-50s, Amy Franklin kicked a goal from a free and the Eagles trailed by only five points in the third term.
Stephanie Cain snapped a crucial goal against the run of play inside the last minute of the quarter, giving the Bombers a 17-point buffer at the final change.
The Eagles again pressed, but could not capitalise in the goal-less final term.
Forward Roberts starred for West Coast, and defender Beth Schilling helped keep them in the game, racking up seven marks.
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