The middle forward was a regular contributor during the Panthers' dynasty, though he did not play in any of their four consecutive premiership triumphs.
He was included in the 17 for the 2024 decider against Melbourne before Scott Sorensen recovered from injury and ousted him from Penrith's fourth consecutive premiership win.
The 33-year-old just felt the time was right and his retirement is not linked with injury or form.
He was contracted for this season but appears to have fallen down the pecking order for first-grade opportunities given the arrivals of Kalani Going and Tom Ale, and the emergence of youngster Billy Phillips.
Panthers football boss Matt Cameron coached Eisenhuth in the now-defunct National Youth Competition and paid tribute to the veteran.
"It's been a privilege to watch his transition from a young player into the professional and respected athlete he is today," Cameron said.
"His work ethic, leadership and commitment to the team helped set the standard for those around him, and he played an important role in the success we've enjoyed in recent years."
Eisenhuth made his NRL debut at Wests Tigers in 2017 under future Panthers coach Ivan Cleary and went on to play 145 NRL games.
He joined the Panthers in 2021 and became a regular of their middle-forward rotation, typically starting from the bench.
Eisenhuth also helped Penrith win the 2022 NSW Cup and State Championship titles during a year of dominance across the grades for the club.
He captained an understrength Panthers side against Canterbury in round 26 last year, in what turned out to be his last NRL game.
Eisenhuth's final professional appearance was for the Prime Minister's XIII in last year's annual clash against Papua New Guinea.
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