Oteri grew up in the Philadelphia suburb of Upper Darby, Pennsylvania (also the hometown of SNL writer/performer Tina Fey). She went to Archbishop Prendergast high school (on the same campus as Monsignor Bonner High School). Moving to Los Angeles at age 25, she worked at A&M Records for four years and eventually joined the famed comedy troupe The Groundlings. It was there that she was noticed by SNL and was hired in 1995 as part of a nearly all-new cast brought in to save the show after its disastrous 1994 season.

Oteri would eventually form a third of the so-called "SNL female power trio" that also included Molly Shannon and Ana Gasteyer and which was responsible, along with Will Ferrell, Darrell Hammond and others, for bringing SNL out of its slump.

She was known for playing perky, upbeat, often hyper characters including cheerleader-wannabe Arianna (one half of The Spartan Cheerleaders), grouchy grandmother Rita DelVecchio, prescription pill-addicted Collette Reardon, and overly perky "Morning Latte" talk show host Cass Van Rye (re-teaming her with "Spartan Cheerleaders" partner Will Ferrell). Her dead-on impressions of Barbara Walters, Mariah Carey, Robin Byrd and Judge Judy also bolstered her fame.

Oteri left SNL in 2000. She has appeared in several movies including Scary Movie, Inspector Gadget, Liar Liar, and Dumb and Dumberer: When Harry Met Lloyd.

Her non-SNL television credits include guest spots on Just Shoot Me and Curb Your Enthusiasm.