Critics gave "Piece of Me" positive reviews, praising its production and defiant lyrics, while citing it as one of the highlights from Blackout. Rolling Stone ranked the song at number fifteen on their list of the 100 Best Songs of 2007. It was also commercially successful, peaking at number one in Ireland and reaching top ten positions in Australia, Austria, Canada, Denmark, Finland, New Zealand, Sweden and the United Kingdom. In the United States, it became the second single from the album to have peaked at the top of the Billboard Hot Dance Club Play chart.
The music video, directed by Wayne Isham, portrayed Spears's life at the time and showed her with her friends disguising themselves in order to confuse the paparazzi. Isham's concept was to have Spears confidently parodying her situation. It received mixed reviews from critics, most arguing her body was digitally altered. The video was nominated in three categories at the 2008 MTV Video Music Awards and won all of them, including Video of the Year. "Piece of Me" was performed at The Circus Starring Britney Spears (2009) and the Femme Fatale Tour (2011).