The Sky Blues on Tuesday confirmed Campuzano had suffered the dreaded injury to his left knee after jumping for the ball and landing awkwardly at training.
Sydney said Campuzano, who is out of contract at season's end, had been ruled out "for a number of months".
The 29-year-old has returned to Spain to have knee surgery then commence his rehabilitation.
"It's one of those things that can happen to any footballer and, unfortunately, this time it's my turn," Campuzano said.
"Of course, I'm disappointed because I was looking forward to the new season, but now my focus is on recovering as well as I can and coming back stronger."
Campuzano's injury leaves Sydney without an experienced senior striker after loanee Apostolos Stamatelopoulos and Patrick Wood both departed in the off-season.
The Sky Blues were already keen to secure another striker but now will have to seriously home in on signing an injury replacement for Campuzano.
Sydney's stocks include youngsters Mathias Macallister and Mitchell Glasson, and new signing Gabriel Popovic.
Campuzano scored four goals and notched three assists in his 24 games last year.
"It's devastating news for Victor because he was working extremely hard and was looking forward to making an impact this year," coach Patrick Kisnorbo said.
"Everyone at the club wishes him the very best with his surgery and recovery.
"Victor is a fantastic person to have around the group.Â
"He's got a really likeable personality, he's popular with everyone at Sky Park and we'll certainly miss having him around the training ground."
