The song reached number one in Mexico, number four on the U.S. Billboard Hot 100 (Lavigne's third single to reach the top ten), number five in New Zealand, number seven in the United Kingdom and number 13 in Canada. "I'm with You" received radio and television airplay in Australia, but it was not officially released there.
In United Kingdom, "I'm with You" was released on March 31, 2003. The song debuted and peaked at #7 on the UK Singles Chart in 2003, becoming her third top ten single on the chart; the song re-entered in UK Singles Chart in the week of 17 December 2011 in #58. It debuted at #6 and peaked at #5 in Ireland, staying in the top ten for six weeks. "I'm with You" reached top five in New Zealand; top ten in Belgium and the Netherlands; top twenty in Sweden, Switzerland, Austria, Germany, Norway, and Denmark as well as reaching the top forty in France. The song re-entered the UK Singles Chart on December 10, 2011 at #58, almost 10 years after the song first charted.
The single's music video, directed by renowned photographer David LaChapelle, involves Lavigne, who is seen alone, trying to find someone. Showing her originally at a party, the video also sees Lavigne pushing a guy when he tries to get with her. Most of the video is shown in slow motion but Lavigne's mouth movements are in sync with the song's vocals. This was achieved by recording the footage while the song was played twice as fast. The video also sees Lavigne walking on the streets and wearing a black jacket. Through the video, she is seen standing behind a snowy bank. At the end of the video, Lavigne walks out of the club with her coat on, kicks out the door and walks away. Much Music named the video one of the "Top 100 Best Videos of All Time".
The arrangement of singles from Let Go, with "I'm with You" as the third, was regarded as "controversial choices", given that "I'm with You" was "thought by some to be the biggest potential smash on the album", and could have established Lavigne as a more mature artist if it was released first. According to Reid, "Some people just really didn't get that. And with the first video, there was some concern that maybe because it's so young and so playful, it might alienate more serious music lovers."KidsWorld called it "the perfect song to drown your sorrows to when that guy from your class breaks your heart."
In 2003 Leama & Moor remixed the song, releasing a remix and a dub.
In September 2010 it was announced that "I'm with You" was to be sampled by Barbadian singer Rihanna. The song is sampled on the track "Cheers (Drink to That)", which was released as a single from Rihanna's fifth studio album, Loud. Lavigne made an appearance in the music video.
On October 11, 2012, the song was performed on The X Factor (U.S.) by Diamond White during the Judges' Houses round.
On November 3, 2012, the song was performed on The Voice U.S. by Cassadee Pope during the Quarterfinals as her "Contestant's Choice". She sang it again during the finals (December 18, 2012), alongside Lavigne, and she tweeted: "Just met my idol. AND sang with her."
In April, 2013, the song was performed by Amber Carrington, on The Voice U.S..