The Sarah Silverman Program is a musical/comedy that journeys into the world of Sarah Silverman where daily life is anything but routine. Silverman plays a character named Sarah Silverman and is joined by her real-life sister Laura Silverman who plays the character of Laura. Rounding out the cast of characters are the geeky gay neighbors Steve (Steve Agee) and Brian (Brian Posehn), and Officer Jay (Jay Johnston).
Sarah discovers that the community group she joins is a radical anti-abortion group; a game of "Dungeons and Dragons" interferes with Steve and Brian's plans for a date night.
Authorities take Sarah's dog Doug away when she is witnessed licking his hindquarters. Distraught, Sarah goes on a quest to redeem herself.
Sarah strongly believes that it is much easier to be a black person in America than it is to be a Jewish person. To prove her point she decides to become black for a day. Meanwhile, Brian and Steve get carried away smoking medical marijuana.
When their mother's grave is vandalized, Sarah and Laura become contestants on their favorite TV show in hopes of winning enough money to replace the tombstone.
Sarah starts a relationship with God who turns out to be needy and insecure. However, she still hopes to show him off at her upcoming high school reunion. In the mean time, Brian and Steve question the origins of their sexuality.
Sarah fires her maid, Dora, believing that she has stolen her beloved Hamburglar doll. When her life slips into filthy disarray, Sarah goes to Mexico to get her maid back, but Dora has since gained unexpected power.
In an attempt to get Sarah to “man up”, Laura falsely informs her that she was born with both a penis and a vagina. Brian and Steve are haunted by the ghost of Mr. Jenkins.
After Sarah's morning brunch at Romanski's is interrupted by a children's book reading, Sarah goes on a crusade of her own to show how easy it is to make children's books and television. Jay and his "anti-Sarah" support group, square off with Sarah on Real Time with Bill Maher. Laura informs Brian and Steve that their balls have an unpleasant odor.
Sarah sues "Home Alone", the movie, for influencing her to accidentally murder her new neighbor. Her eloquent case about the dangerous influence of entertainment leads her to the position of official censor of Valley Village television. Brian seeks revenge on a bird who repeatedly shits on his head.
Sarah is sick of hearing about the upcoming mayoral election, so she amuses herself by campaigning for a fake write-in candidate whom she calls, "May Kadoody." An actual May Kadoody steps forward when her name is, shockingly, announced as the winner. Kadoody outlaws brunch and gay marriage, interfering with Steve's dream of marrying Brian.
Sarah reconnects with her childhood imaginary friend, Troy, who lures into a life of sex and drugs. After Brian refuses to let Steve play in his band, Steve creates a song that mocks Brian, and gains immense popularity on the internet.
Sarah has the mistaken epiphany that she is retarded, and tries to use her disability to inspire people. Brian and Steve accidentally bump heads while trying to pick up a magical dragon phone and switch bodies.
Sarah and Steve go to a jam band concert where Sarah convinces all of the fans that they are tripping.
Sarah narrates the story of Steve creating a baby robot.
Brian and Steve have a stand-off to decide who will do the laundry.
Laura and Sarah mount dueling Holocaust memorials.
Sarah gets arrested for drinking (cough syrup) and driving. After she is released from jail Sarah discovers the attraction between her sister Laura and the arresting officer. Meanwhile Brian tries to convince his partner Steve that he is bisexual.
Sarah invites a homeless man into her home to prove she is a caring person. Meanwhile Brian learns karate, but fails to use it in dire straits.
Sarah decides to take an AIDS test to cure her case of the blahs. Meanwhile Jay celebrates his birthday with a party.
Sarah becomes an adviser to a local beauty-pageant contestant. She encourages a young girl to enter the pageant in order to fulfill her own childhood dreams. Meanwhile, Steve's behavior in a police car result in unforeseen consequences.
Sarah tries to explore her own sexuality. Meanwhile Brain and Steve bicker over a soft drink.
Sarah searches for AA batteries so that she can use her remote to turn off a television benefit for needy children. While on her search, Sarah loses a farting contest and has a sexual encounter with God.