The Best of Brandy was appreciated by contemporary critics who noted the creativity of Norwood's back-catalogue. It debuted at number 27 on the Billboard 200 albums chart, selling about 26,000 units in its opening week, and became a top thirty success in Australia and the United Kingdom. In international territories, the second US single from Afrodisiac, "Who Is She 2 U" was released as a single in support of The Best of Brandy.
On November 1, 2004, four months after the release of her fourth studio album with Atlantic Records, Brandy's publicist Courtney Barnes announced that the singer had requested and was granted an unconditional release from her recording contract with the music label, her record company since 1994, as Norwood was at "a place where [she wants] some change in her life [and] wanted to move on" musically. Brandy was subsequently asked to complete her contract with the release of a greatest hits collection, a plan which she considered a true compliment and showcase for her development as a recording artist over ten years. "I'm really proud of it," Brandy said about the compilation album the following year. "When you get a chance to step back, you notice all these great things you've done and all these great people that you've worked with. The album is a celebration of me being in the industry for so long, and I'm still going." In addition, Norwood declared her satisfaction with the conclusion of her Atlantic era: "I just thought it was a great idea – to put 18 songs together of the best of everything that I’ve done made me feel really good. And also, it is giving me a reason to move on from everything I’ve done. I’m excited about putting it out and also putting it behind me."
The Best of Brandy received generally favorable reviews from music critics. Andy Kellman of Allmusic gave the compilation four and a half out of five stars and commented that "the disc is straightforward and rather thorough in its makeup, compiling almost all of Brandy's charting singles, [and] though the last two albums evidently didn't produce big singles, they're just as strong and fresh as the first two — so this set, unlike so many other anthologies from her contemporaries, hardly confirms dwindling creativity or popularity." Thomas Inskeep from Stylus magazine commended that Norwood "helped soundtrack highs and lows, especially highs, with your so fresh/so clean stable of killer singles. Now that they’re collected like this, it’s like my own personal time capsule. Here’s to another decade, Brandy. As Aaliyah sang, you’re more than a woman, and the pop/R&B landscape is richer for your presence in it. Thanks." He gave the album an "A" rating.
In his review for Slant magazine, Sal Cinquemani criticized both Warner Music and Atlantic for "botching the promotion of her last studio album [Afrodisiac]" and Norwood's subsequent drop. He was however positive with the album's track lisiting, stating: "The collection is capped off with non-album tracks like the #2 hit "Sittin' Up in My Room" and covers of Michael Jackson's "Rock with You" and Phil Collins's "Another Day in Paradise," which, though it's not exactly a labor of love for Brandy's longtime label home, makes The Best of a must-have for the hardest-core Moesha fans." He rated the compilation three and a half out of five stars. Less enthusiastic, Chris Taylor from MusicOMH felt that album proved that Norwood was "a fine wine that has never quite fully matured [...]The overall result is a middling collection which ultimately leaves one frequently fast-forwarding, wondering what could have been."
In the United States, The Best of Brandy debuted at number 27 on the Billboard 200 and number 11 on the Top R&B/Hip-Hop Albums chart, selling about 26,000 units in its opening week. It remained five weeks within the chart and was left uncertified by the RIAA. Internationally, the compilation album entered the top thirty in Australia and the United Kingdom only, where it reached number 25 and 24 respectively, but enjoyed short runs on the national albums charts. In addition, the album reached number 92 on the European Top 100 Albums chart.