(written from a Production point of view)
Starting her acting career on Saturday Night Live (including episodes hosted by Patrick Stewart and Kelsey Grammer), with fellow VOY guest star Michael McKean as a castmate for the latter half of the year, she has since made guest appearances in Crank Yankers, Drawn Together, Futurama, Frasier (with Kelsey Grammer and Penny Johnson), JAG (as the assistant of a character played by Gary Graham), and Monk (with Billy Burke, Nicole Forester, and Stanley Kamel). She has also made movie appearances in The Bachelor, Say It Isn't So, Heartbreakers, Evolution, There's Something About Mary, The Aristocrats, and Sarah Silverman: Jesus is Magic. These last two were a documentary and a concert film, respectively, which showcase Silverman's edgy and often controversial brand of comedy; she also wrote and performed several original songs in Jesus is Magic.
Silverman also starred in the Fox Network's short-lived 2000 comedy television series Greg the Bunny (with Bob Gunton).
In 1997, she starred in Who's the Caboose? alongside Andy Dick and H. Jon Benjamin. She starred with Star Trek: Deep Space Nine guest star Stephen Yoakam, as well as Larry Drake and Bruce Bohne, in the 1998 movie Overnight Delivery.
She had her own show on Comedy Central called The Sarah Silverman Program. The episode "Batteries" of that series starred fellow Voyager alumnus Tucker Smallwood as God. The series premiered in 2007 and was canceled in 2010.
In 2007, she hosted the 2007 MTV Movie Awards. In a brief interview with Entertainment Weekly as a lead-up to the MTVMAs, she was asked: "You guest-starred on two episodes of Star Trek: Voyager. What's one misconception about Trekkies that needs clearing up?" Her response was, "Oooh! This is totally true! Since I did that in 1996, one thing I learned about sci-fi nerds is the majority – and you're not going to believe this because it's not portrayed that way in movies – are black. More black people than white people recognize me from Star Trek. Black people love sci-fi. That's a serious fun fact. You're welcome." 
Romantically linked with TV host Jimmy Kimmel for several years, Silverman wrote and performed the obscenity laced song "I'm F--king Matt Damon" for his series Jimmy Kimmel Live!, for which Silverman received a Creative Arts Emmy Award in 2008. 
Since 2011, Silverman has provided the voice of Ollie Pesto in the Fox network comedy series Bob's Burgers. The character's twin brother Andy is played by Silverman's actual sister, Laura. Silverman was also the voice of Vanellope in Disney's acclaimed 2012 animated film Wreck-It Ralph.
In 2015, Silverman played Lainey Brooks in the drama I Smile Back, co-starring Chris Sarandon. For this role, Silverman received a 2016 Screen Actors Guild Award nomination as Outstanding Performance by a Female Actor in a Leading Role.  In 2017, Silverman portrayed feminist executive Gladys Heldman in the tennis biopic Battle of the Sexes, co-starring Mark Harelik, Wallace Langham, Matt Malloy, and Tim Ransom.