“Trust, betrayal and the inability to consent – that’s what this case is about,” a prosecutor told the court in Pennsylvania.
Mr Cosby is on trial for allegedly molesting a woman who was seeking career advice in 2004.
Dozens of other women accuse the 79-year-old entertainer of sexual assault.
Assistant District Attorney Kristen Feden told jurors on Monday: “This is a case about a man – this man – who used his power and his fame and his previously practised method of placing a young, trusting woman in an incapacitated state so he could sexually pleasure himself, so she couldn’t say no.”
As Mr Cosby sat a few feet away, the assistant district attorney urged jurors to look beyond his role as the dad on the hit 1984-1992 television sitcom The Cosby Show.
That wholesome TV image would be “shattered”, she said, accusing the entertainer of “heinous crimes”
Defence attorney Brian McMonagle countered that Mr Cosby is the victim of false accusations.
“Today I get a chance, with your help, to right a wrong,” he told jurors.
“I get a chance, with your help, to protect a man from the destruction of the rest of his life.”