Her maternal great-great grandfather was william A. Feilds, an African-American legislator in the Tennessee House of Representatives. Her mother Helen Tinch met her Father Milton Augustine Williams Jr. (1935–2006) while both were music education students at Fredonia State Teachers College in the late 1950s. They both became elementary school music teachers after marriage, though their teaching positions were in separate districts. Milton also served as the assistant principal of his school for an extended period of time.

Williams is most often referenced and publicly recognized simply as "Vanessa Williams." There is, however, occasional confusion with the similarly named Actress Vanessa A. Williams, who is just two months younger. It has been reported that Williams first became aware of Vanessa A. in the 1980s when her New York University registrar told her that another, similarly aged student with the same name and from the same state had applied. When Williams appeared as Miss America in a Macy's Thanksgiving Day Parade, Vanessa A. accidentally received her check for the appearance, which she returned.

A child of music teachers, Williams grew up in a musical household, studying classical and jazz dance, French horn, piano, and violin. She was offered the Presidential Scholarship for Drama to attend Carnegie Mellon University during the college application period, (one of 12 students to receive it) but decided instead to attend Syracuse University on a different scholarship. Thus, in 1981, Williams joined Syracuse's College of Visual and Performing Arts, Department of Drama as a musical theater major. She stayed at Syracuse through her sophomore year until she was crowned Miss America 1984 in September 1983.

Williams has had a successful career in television. Her first television appearance was on a 1984 episode of The Love Boat followed by guest appearances in a number of popular shows. In 1995, Williams starred as Rose Alvarez in a television adaptation of the 1960 Broadway musical Bye Bye Birdie and portrayed the nymph Calypso in the 1997 Hallmark Entertainment miniseries The Odyssey. In 2001, Williams starred in the Lifetime cable movie about the life of Henriette DeLille, The Courage to Love and in 2003, Williams read the narrative of Tempie Herndon Durham from the WPA slave narratives in the HBO documentary Unchained Memories: Readings from the Slave Narratives. In 2006, Williams received considerable media attention for her comic/villainess role as former model/magazine creative Director turned editor-in-chief Wilhelmina Slater in the ABC comedy series Ugly Betty. Her performance on the series resulted in a nomination for outstanding supporting Actress at the 59th Primetime Emmy Awards and in 2008 and 2009, she was nominated in the outstanding supporting Actress in a comedy series category for Ugly Betty. Williams next joined the cast of Desperate Housewives for its seventh season, where she portrayed Renee Perry, an old college "frenemy" of Lynette Scavo (Felicity Huffman). In 2016, she joined the cast of The Librarians, as recurring villainess General Rockwell. She is scheduled to star as Maxine on the VH1 television series Daytime Divas in June 2017.

Williams began her career on stage in the 1985 production, One Man Band, as one of "the women." She followed it in 1989 as "Laura" in Checkmates.

Williams has been married three times. She married her first husband, Ramon Hervey II, at St. Francis Xavier Catholic Church in 1987 just a few years after giving up her crown, and gave birth to her first child at this time. Hervey was a public relations specialist who had been hired to resuscitate her career after her resignation as Miss America in July 1984. They have three children (Melanie, Jillian Hervey, and Devin) and divorced in 1997. She then married NBA basketball player Rick Fox in 1999. They have one daughter, Sasha Gabriella Fox, and divorced in 2004. In 2015, Williams married Jim Skrip, a businessman from Buffalo, New York.

Williams rebounded from the scandal with a successful career as a singer and Actress. In 1988, she released her debut studio album The Right Stuff whose title single saw moderate success before "Dreamin'" peaked at number 8 on the Billboard Hot 100 chart in the United States. Her second and third studio albums, The Comfort Zone (1991) and The Sweetest Days (1994), saw continued commercial success and for which she received multiple Grammy Award nominations, including for her number-one hit and signature song, "Save the Best for Last". Her most recent studio albums include Everlasting Love (2005) and The Real Thing (2009).

Her second album The Comfort Zone became the biggest success in her music career. The lead single "Running Back to You" reached top twenty on the Hot 100, and the top position of Hot R&B/Hip-Hop Songs chart on October 5, 1991. Other singles included "The Comfort Zone" (#2 R&B), "Just for Tonight" (#26 Pop), a cover of The Isley Brothers' "Work to Do" (#3 R&B), and the club-only hit "Freedom Dance (Get Free!)." The most successful single from the album, as well as her biggest hit to date, is "Save the Best for Last". It reached No. 1 in the United States, where it remained for five weeks, as well as No. 1 in Australia, the Netherlands, and Canada, and was in the top 5 in Japan, Ireland and the United Kingdom. The album sold 2.2 million copies in the U.S. at its time of release and has since been certified triple platinum in the United States by the RIAA, gold in Canada by the CRIA, and platinum in the United Kingdom by the BPI. The Comfort Zone earned Williams five Grammy Award nominations.

Williams served as the host of the 1994 Essence Awards, co-host of Carnegie Hall Salutes the Jazz Masters: Verve Records at 50, host of the 1998 NAACP Image Awards, host of the 2002 documentary, It's Black Entertainment, host of The 6th Annual TV Land Awards in 2007, host of the 36th Annual Daytime Emmy Awards in 2009, and finally host of the documentary Dreams Come True: A Celebration of Disney Animation (2009).

Other releases include two Christmas albums, Star Bright in 1996, and Silver & Gold in 2004; Next in 1997, and Everlasting Love in 2005, along with a greatest-hits compilation released in 1998, and a host of other compilations released over the years. Notable chart performances from subsequent albums, motion picture and television soundtracks have included the songs "Love Is", which was a duet with Brian McKnight, the Golden Globe- and Academy Award-winning "Colors of the Wind", "Where Do We Go from Here?", and "Oh How the Years Go By".

Williams has also appeared in a number of feature films. She received a NAACP Image Award for Outstanding Actress in a Motion Picture for her portrayal of Teri Joseph for the 1997 feature film Soul Food. In 2007, she starred in the independent film My Brother, for which she won Best Actress honors at the Harlem International Film Festival, the African-American Women in Cinema Film Festival, and at the Santa Barbara African Heritage Film Festival. She also notably co-starred with Arnold Schwarzenegger in Eraser, Samuel L. Jackson in the 2000 remake of Shaft, the characters from Sesame Street in The Adventures of Elmo in Grouchland (as the Queen of Trash), and with Miley Cyrus in Hannah Montana: The Movie.

She received a star on the Hollywood Walk of Fame on March 19, 2007.

Twenty-five years later in May 2008, Syracuse granted Williams a Bachelor of Fine Arts degree. According to Syracuse News, "Williams earned the remaining credits for her degree through industry experience and her substantial performances on stage and screen." Williams also delivered the 2008 convocation address, telling Syracuse seniors to "treasure this moment. These days are irreplaceable and are the beginning of the rest of your life."

Williams is a spokesmodel for Proactiv Solution, and was the first African-American spokesmodel for L'Oréal cosmetics in the late 1990s. She appeared on Who Wants to Be a Millionaire in 2000 as a contestant, and once again on August 10, 2009, as a Celebrity guest during the show's 10th anniversary prime-time special editions, winning $50,000 for her charity.

Williams is also involved with a number of humanitarian causes. She is a supporter of gay rights and same sex marriage, and in 2011 she participated in a human rights campaign entitled “New Yorkers for Marriage Equality". She is also partnered with Dress For Success, an organization that provides professional attire for low-income women, to help support their job-search and interview process. In addition, Williams is involved with The San Miquel Academy of Newburgh, a school for boys at risk.

Williams and her mother Helen co-authored a memoir entitled You Have No Idea, published in April 2012. In the book, Williams discusses her childhood, rise to fame, and personal struggles (including life with type 1 diabetes), including the fact that she was sexually molested by a woman when she was 10 years old. She also spoke candidly about having an abortion while she was in high school.

In March 2016, Williams launched her own clothing line, V. by Vanessa Williams for EVINE Live.