With O'Neill's order, the trial will now rest more heavily on Constand's credibility.
"There is an obvious value to the prosecution when you have numerous accusers. That alone adds tremendous weight to the case," said lawyer Joseph McGettigan, a prosecutor in the Penn State sex abuse scandal.
The ruling could also shave weeks off the trial.
Cosby, who is free on $1 million bail, could get 10 years in prison if convicted. He is expected in court again Monday to ask that the jurors be selected from another county because of the heavy publicity.
Prosecutors compiled the list of 13 potential witnesses from the nearly 50 women who have come forward in recent years to say they were drugged and molested — a barrage that destroyed Cosby's good-guy reputation as the star of TV's Cosby Show in the 1980s.
His lawyers objected to the testimony about "prior bad acts," saying that in some cases the sex was consensual, while others involved models and actresses falsely accusing Cosby to gain money or attention.
His attorneys also argued that some of the allegations were so vague — with some of the women unsure of when the alleged encounters even took place — that it would be impossible for Cosby to defend himself.
While the ruling is a big victory for Cosby at his trial, it could deprive him of grounds for appeal if he is convicted. In 2015, a Pennsylvania appeals court threw out a Roman Catholic Church official's conviction because the jury was allowed to hear from 23 priest-abuse victims who were not directly part of the case.
"It's the best of times and the worst of times for Cosby. It gives the defendant the opportunity to try the case that should be tried, the lone accuser," said defense lawyer William J. Brennan, who was involved in the church case. "If it doesn't go his way, he probably is limited on appellate issues. However, I'd take this, hands down, over the alternative."
The ruling is one of two key pretrial issues in the case. The judge earlier ruled that the jury can hear Cosby's damaging testimony from Constand's 2005 lawsuit against the comedian.
Cosby's deposition runs to nearly 1,000 pages and covers a string of extramarital liaisons dating to the 1960s. It was the release of the sealed testimony in 2015 that led prosecutors to reopen the case.
Constand told police he gave her three unmarked pills and then penetrated her with his fingers as she drifted in and out of consciousness. The comedian has said the sexual contact was consensual.
The additional accuser who can testify worked for one of Cosby's agents and had known the entertainer for six years when he invited her to lunch at his bungalow at the Bel Air Hotel to discuss her career plans.
She said he was in a robe and slippers when she arrived and offered her wine and a pill that she consumed after he assured her it was safe. She said he then sexually assaulted her on his bed.
Among the other accusers who won't be allowed to testify, one said she was an aspiring actress when Cosby assaulted her at a home near Reno, Nevada, in 1984. Another said Cosby drugged and assaulted her in the late 1960s after befriending her and her 9-year-old son.