Long was born in Brooklyn, New York, U.S. to Talita, a teacher and printmaker, and Doughtry "Doc" Long, a high school teacher and poet. Long is of Afro-Trinidadian descent. Her stage name, Nia, is one of the seven days of Kwanzaa, which means "Purpose" in Swahili. Her parents divorced when Long was two years old, and she and her mother moved to Iowa City, Iowa, where her mother studied fine arts. They subsequently moved to a South Los Angeles neighborhood when Long was seven. Long's father currently resides in New Jersey in the City of Trenton. Long's half sister is comedienne Sommore, star of The Queens of Comedy.
Long attended the Roman Catholic school St. Mary's Academy and studied ballet, tap, jazz, gymnastics, guitar and acting. She graduated from Westchester High School in 1989. Due to the lack of employment opportunities in the arts in Los Angeles when Long and her mother first arrived there, Long's mother took various low-paying jobs (despite having two master's degrees). The family suffered through financial struggle for years.
For 30 years, Long was instructed by acting coach Betty Bridges, better known as the mother of Diff'rent Strokes star Todd Bridges. Her first notable role was a three-year contract role as Kathryn "Kat" and Speakes on the soap opera Guiding Light. Long portrayed Kat from 1991 to 1994. From 1994 - 1995, she played Will Smith's girlfriend and fiancée Beulah "Lisa" Wilkes on The Fresh Prince of Bel Air. Jada Pinkett-Smith was originally supposed to play Lisa, but was too short for the role (opposite a 6'2" Will Smith), thus leaving Nia to take the part. In 2003, she joined the cast of the drama Third Watch, where she played NYPD Officer Sasha Monroe, continuing until the series finale in 2005. In 2005 and 2006, Long appeared on Everwood, and appeared on Boston Legal during its 2006-2007 season.
She appeared in supporting roles in a number of movies such as Boyz N the Hood, Friday, and Made in America. Long played a leading role, or a member of the primary ensemble, in several films, including Soul Food, Love Jones, Boiler Room, Big Momma's House, Are We There Yet?, and The Best Man. Ice Cube has starred with her in four films, while Regina King has starred with her in two. Long starred alongside Michael Beach in Soul Food and in the TV series Third Watch.
She appears in the video for Kanye West's "Touch The Sky". She directed Yolanda Adams's music video for "This Too Shall Pass". Long was voted one of the 50 most beautiful people in the World 2000 by People. She won a NAACP Image Award for Outstanding Actress in a Drama Series in 2004 for her performance on Third Watch. Long co-directed and appeared in Ashanti's music video, "Baby". She also made a guest appearance on the successful sitcom Living Single during its first season.
With regard to being a working mother, she says "she is up for the challenge so long as it does not require disturbing her family's well-being". "If I'm gonna hustle, I want to hustle in one place... I uprooted everything, moved to New York for two years, moved back and it was great but I really, I'm enjoying the stability."
Long and her former long-time boyfriend and fellow actor Massai Z. Dorsey have a son, Massai Zhivago Dorsey II, born on November 26, 2000. Dorsey and Long were engaged to be married, but ended their relationship.