The two fugitives may already have left the country, after the guard helped the prisoner break out of jail near Zurich on Monday night, Zurich cantonal police police said in a statement.
The 27-year-old Syrian man had been sentenced to four years in the Limmattal jail in Dietikon for rape.
The man, identified as Hassan Kiko, told a Swiss newspaper (the Thurgauer Tagblatt) in 2011 that he fled Syria after being imprisoned for three months by the Assad regime.
According to initial police findings, the guard with whom he fled is 32 years old, though her name and nationality were not released.
The two fled the prison together, the statement said, and police launched a search operation as soon as they learnt of the jailbreak.
Correctional authorities believe the pair may have fled to Italy.
"It is clear that the human factor played a role in this affair," Rebecca de Silva, a spokeswoman for Zurich's cantonal correctional department told 20 Minuten newspaper.
"The guards are in contact with the inmates and look after them," she is quoted as saying.
"A certain intimacy is created among them."
The escape is the first on record at the Limmattal prison, which opened in the Zurich suburb in 2010.