The five-time Super League champions have lost their last four games, and are winless in five, and Simmons has now been moved on following Saturday’s 12-8 defeat at Bradford, ironically coached by Simmons’ predecessor Mick Potter.
Mike Rush has been placed in temporary charge as acting head coach, and will be assisted by Saints legend Keiron Cunningham.
Simmons’ assistant, Kieron Purtill, has also left the club.
Chairman Eamonn McManus stated: “Our season has got off to a difficult start and it is best to make change sooner rather than later. We have every faith in Mike Rush and Keiron Cunningham. They each know the Club inside out and have all the experience together to take us forward.
“I would like to go on record to pay genuine tribute to Royce Simmons. He is a fantastic person, and of absolute character and integrity, who has given everything to the Club.
“I am sure that everyone at the Club joins me in thanking him sincerely for all his work and dedication and to wish him and his family well for the future.
“Our sentiments are the same with Kieron Purtill. Force of circumstance has reconstituted change.”
In his first and only full season at the club, Simmons guided Saints to a sixth consecutive Grand Final, where they were beaten by Leeds, for the fourth time in five years.
A former coach of Hull, Simmons was an international and State of Origin hooker during his playing days, cutting his coaching teeth at Penrith Panthers, before spending eight years as assistant coach to Tim Sheens at Wests Tigers.
Saints have managed just two wins in 2012, against London and Salford in the first two rounds of the season.
They then drew 36-36 against Hull KR, before suffering defeats against Catalan, Huddersfield, Hull and Bradford.