The 23-year-old struck twice in the first half to secure a 4-1 win in front of a record 25,125 crowd at GIO Stadium in Canberra on Monday night.
Alongside Arsenal striker Caitlin Foord, Sayer terrorised the Argentinian defence with her pace and incisive runs.
You could scarcely believe that, not too long ago, a devastating ACL injury had her questioning whether she would be able to fully recover.
"I worked really hard to get to this point, and I think it showed on the field, the work that I put in and the time," she said.
"There was a point in my rehab where I didn't even think I'd be able to walk properly again.
"So, yeah, the biggest thing is just for me to be on the field, and anything extra is just a bonus."
The Matildas dominated possession and scoring opportunities, as the midfield pairing of Kyra Cooney-Cross and Clare Wheeler outclassed their South American opponents.
But some nervy moments at the back between Steph Catley and Natasha Prior gave the tourists a sniff, with the dangerous Kishi Nunez a persistent threat.
Their sixth-straight victory on home soil is a happy parting gift for Sermanni in his third stint in charge of the national side, and a promising omen for his replacement, former Lyon boss Joe Montemurro.
Sayer opened the scoring in the 14th minute, popping up at the far post to ram home a deflected volley after a searching Kahli Johnson cross evaded a sea of players.
Argentina struggled to play through the Matildas' high press and failed to exert any real pressure when the home side had the ball.
But a seemingly innocuous through-ball left Prior all at sea, and the door open for Nunez to steal in behind unchecked and curl the ball past a diving Teagan Micah, ending a run of four home clean sheets for the Matildas.
The response was swift, though. Foord, who menaced defenders all night, nicked the ball near the halfway line before releasing Sayer .
From an unfriendly angle, Sayer picked out the far corner past the outstretched gloves of goalkeeper Solana Pereyra.
As the Argentinians tired in the second half, the game opened up for the Matildas.
Sayer nearly sealed a hat-trick in the 54th minute fter being sent through by Catley but sprayed her shot from the right high and wide.
Holly McNamara nearly scored her first Matildas goal in the 57th minute but the prolific Melbourne City forward's volley from eight yards was smartly stopped by Pereyra.
After being subbed on for Sayer in the second half, hometown hero Michelle Heyman had a hand in the Matildas' third goal in the 71st minute when she found herself one-on-one with the goalkeeper.
However, Pereyra poked the ball away from Heyman's feet, only for it to be turned in by Emily van Egmond.
Heyman finally got her goal in the 83rd minute after Foord again pressured the Argentinian defence into a mistake on the edge of their box, with the veteran squeezing the ball in off a defender from a tight angle.
An early concern for Montemurro will be the fitness of youngster Kahli Johnson, who limped off late in the first half.
But he takes over a Matildas side in much healthier shape than when Sermanni did after a disappointing Olympics campaign.
"I felt, when I came into squad, the confidence and the belief in the players, collectively and individually, was at a fairly low ebb," Sermanni said.
"I think what's happened in that time is that we've been able to bring back a little bit more confidence in the squad.
"But also able to start to bring players who have been kind of on the outside of the squad into believing that they feel part of the squad - players like Amy."
