Pfeiffer was born in Santa Ana, California, the second of four children of Richard Pfeiffer, an air-conditioning contractor, and Donna (nee Taverna), a housewife. She has one elder brother, Rick (born 1955), and two younger sisters, Dedee Pfeiffer (born 1964), a television and film actress, and Lori Pfeiffer (born 1965). Her parents were both originally from North Dakota. Her paternal grandfather was of German ancestry and her paternal grandmother was of English, Welsh, French, Irish, and Dutch descent, while her maternal grandfather was of Swiss-German descent and her maternal grandmother of Swedish ancestry.

Pfeiffer's subsequent career choices have met with varying degrees of success. After The Age of Innocence, she played the role of Laura Alden opposite Jack Nicholson in Wolf (1994), a horror film that garnered a mixed critical reception. The New York Times wrote: "Ms. Pfeiffer's role is underwritten, but her performance is expert enough to make even diffidence compelling". The movie grossed US$65 million (equivalent to $107.3 million) at the domestic box office and US$131 million worldwide (equivalent to $216.3 million). Her next role was that of high school teacher and former US Marine LouAnne Johnson in the surprise box office hit Dangerous Minds (1995), which was co-produced under Pfeiffer's film production company Via Rosa Productions. She appeared as her character in the music video for the soundtrack's lead single, "Gangsta's Paradise" by Coolio (featuring L.V.), which was used by the producer Jerry Bruckheimer for television advertising. A 60-second version was aired on music channels, while a 30-second cut was aired in the rest of the networks. The song won the 1996 Grammy Award for Best Rap Solo Performance, and the video won the MTV Video Music Award for Best Rap Video.  In 1996, she turned down the Golden Globe Award-winning role of Eva Peron in the biopic Evita, which went to Madonna. Pfeiffer then portrayed Sally Atwater in the romantic drama Up Close & Personal (1996) opposite Robert Redford. The film's screenplay, co-written by husband and wife team John Gregory Dunne and Joan Didion, was intended to be a biographical account of the career of news anchor Jessica Savitch, but the final version had almost nothing to do with Savitch's life, leading Dunne to write an expose of his eight-year battle with the Hollywood producers, Monster: Living Off the Big Screen.  She took the role of Gillian Lewis in To Gillian on Her 37th Birthday (1996), which was adapted by her husband David Kelley from Michael Brady's play of the same name. Pfeiffer and her producing partner Guinzburg were on a winning streak of producing three back to back films next under their Via Rosa Productions header that included, One Fine Day (1996), A Thousand Acres (1997) and The Deep End of the Ocean (1998). She served as an executive producer and starred as the divorced single mother architect Melanie Parker in the romantic comedy One Fine Day (1996) opposite George Clooney, Subsequent performances included Rose Cook Lewis in the film adaptation of Jane Smiley's Pulitzer Prize-winning novel A Thousand Acres (1997) with Jessica Lange and Jennifer Jason Leigh; Beth Cappadora in The Deep End of the Ocean (1998) about a married couple who found their son who was kidnapped nine years ago; Titania the Queen of the Fairies in A Midsummer Night's Dream (1999) with Kevin Kline, Rupert Everett and Stanley Tucci; and Katie Jordan in Rob Reiner's comedy-drama The Story of Us (1999) opposite Bruce Willis.

Did she win any awards?