Protesters read the names of the dozens of women who have come forward accusing the actor and comedian of sexual assault.
"We don't want a serial rapist in our city and we're here to tell the people who are giving him money exactly who he is and what he has done," said protest organizer Rachel Perry-Crook.
"In America, it's supposed to be innocent until proven guilty. Not, in America, guilty until proven innocent," said a woman attending the show.
Cosby has not been charged with a crime, despite allegations from a string of women who say they were drugged and sexually assaulted or raped. Some of the claims date back to the 1960s.
Earlier in the day, two new accusers came forward. They spoke to the media alongside attorney Gloria Allred in Los Angeles.
"At some point I didn't really wake up, but came to a little, and the first thing I saw was Bill Cosby's face not far above me and we were both naked. He was inside me and touching me," said accuser Margie Shapiro.
"I believe that Bill Cosby is a sexual predator and a disgusting human being to not acknowledge what he's done to so many girls and women in his life," said accuser Sunni Welles.
Cosby's attorney has denied the numerous previous allegations.
Back in Baltimore, the Lyric Opera House was only about half full as the legendary performer entered the room. He was welcomed on stage to applause after which the media was quickly ushered out. Minutes later, we're told one audience member yelled out 'What about the women?' but was then removed by security.
Cosby's tour heads to West Virginia next, though shows were canceled in a number of cities.