Union made her feature acting debut in 1999's "She's All That", serving as the friend and conscience for Freddie Prinze Jr.'s sensitive but deceitful hero with a small but pivotal role. That same year, she played a far more sinister character as the back-stabbing best friend of Bianca (Larisa Oleynik) in "10 Things I Hate About You", the teen take on "The Taming of the Shrew". Though the actress was by then in her mid-twenties, she was still very believable as a teen, even as the particularly immature and petty Chastity. These youthful looks would work to her advantage, as the spate of teen-aimed fare seemed nowhere in sight. The critically acclaimed romantic drama "Love & Basketball" (2000) gave Union the opportunity to play a single-minded basketball groupie after hot property Q (Omar Epps), while that same year's similarly sports-themed "Bring It On" made her the center of attention. An athlete from early childhood, Union embraced the opportunity to take on a more physical role, but even she found the training involved in being a cheerleader surprisingly rigorous. Rising admirably to the challenge, the actress brought her style and spark to the role of Isis, an inner-city cheerleader whose squad has the moves but not the finances to win the national championship. Making the most of her role and never descending into a typical "underprivileged fighter with a chip on her shoulder" portrayal, Union lit up the screen in "Bring It On", and her magnetism as well as that of comparably talented co-star Kirsten Dunst was no doubt responsible for the film's surprisingly lucrative box-office run.

Union put aside teen roles for a regular stint on the troubled CBS medical drama "City of Angels" (2000), playing the lead female in a largely African-American ensemble cast. The following year she made history when her featured guest role as the love interest of both Joey (Matt LeBlanc) and Ross (David Schwimmer) unfathomably marked the first time a black actor was featured on the New York City-set sitcom "Friends" in its seven-season run. The following week, on March 23, 2001, "The Brothers" opened. An African-American ensemble piece, the film centered around four successful young professional men and their various attitudes towards relationships. Union played Denise Johnson, whose respective gentleman was a ridiculously commitment-phobic Morris Chestnut. Though Denise was originally written as a meek, resigned character, director Gary Hardwick advised the actress to bring her own fire to the role, and Denise became a strong-willed and assured young woman whose independent spirit and alluring self-sufficiency just might change the notorious player's ways.

A supporting turn in the 2001 comedy "Two Can Play That Game" returned Union to the big screen that fall, while projects including the comedy "Welcome to Collinwood"--in which her fleeting appearance nevertheless made a major impression--and the college-set thriller "Abandon" (both released in 2002) would keep her on the scene for a while to come. A favorite among critics and moviegoers alike, Union was poised to be a breakout star although her down-to-earth attitude toward show business would indicate that she didn't look to superstardom as the key to happiness.

In 2003, Union joined rap icon LL Cool J for the comedy feature "Deliver Us From Eva" (2003). Union, as the title character Eva, plays an up-tight young woman who finds joy in meddling in her younger sisters' love life. Also that year, Union was cleverly cast in the sequel "Bad Boys II" (2003) opposite Martin Lawrence and Will Smith as Lawerence's lovely sister. Union's character is not only in danger at the crux of the plot, she also has an opportunity to get romantically entangled with Smith and comedically opposed to Lawrence, developments that served to introduce the actress' distinctive charms to an even wider audience in her first "blockbuster" starring role. After starring opposite Jaime Foxx in the romantic comedy “Breakin’ All the Rules” (2004), she played Alice Kramden to Cedric the Entertainer’s Ralph Kramden in the rehash of the famed 1950’s sitcom, “The Honeymooners” (2005). Though promising a fresh take on an oldie-but-goodie, the film was blasted by critics who cited a lack of chemistry between characters, a subservient bow to political correctness—particularly with Kramden’s famous threat to send Alice to the moon—and a dearth of laughs despite overwhelming comedic talent. She then took on a role in the ABC remake of the classic supernatural TV series "Night Stalker" (2005) as Perri Reed, the all-too-normal partner to Carl Kolchak. Union was then caught up in a rare mini-controversy in fall 2005 when he publicist circulated an email urging entertainment industry types to boycot the Hollywood night spot Club Mood, alleging that the club refused to host Union's 33rd birthday party because of her race. The club's owner denied the allegations and the p.r. company later issued an apology. Within a week of that incident, it was announced that Union had split from her husband of almost five years, running back Chris Howard.