Four of the alleged offences are said to have taken place in London, while the other is alleged to have happened in Gloucestershire, in the southwest of England.
Robert Ainslie, head of the UK Crown Prosecution Service's Special Crime Division, said: "The CPS has authorised criminal charges against Kevin Spacey, 62, for four counts of sexual assault against three men.
"He has also been charged with causing a person to engage in penetrative sexual activity without consent. The charges follow a review of the evidence gathered by the Metropolitan Police in its investigation.
"The Crown Prosecution Service reminds all concerned that criminal proceedings against Mr Spacey are active and that he has the right to a fair trial."
The Met opened an investigation into the House of Cards star in 2017.
Spacey was interviewed under caution by the police in 2019.
His House of Cards character, Frank Underwood, had to be killed off after he was booted from the series as allegations emerged.
Spacey was ordered to pay the studio that created the show $43.7 million last year over breach of contract following sexual harrassment claims.
The production company claimed it incurred extra costs as it had already started filming parts of a new series before Spacey had to be cut out.
The former A-lister has a new film coming out, Peter Five Eight, in which he plays a serial killer.
Spacey won the Academy Award for best actor for his performance in American Beauty, and also won the best supporting actor Oscar after starring in The Usual Suspects.
He also starred in Seven, LA Confidential and Baby Driver.