The song reached number four on the US Billboard Hot 100, as well as reaching the top ten in nine other countries, thus making it Lavigne's third single to reach the top ten. "I'm with You" received radio and television airplay in Australia, but it was not officially released there.
The song received critical acclaim from music critics. 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 United Kingdom, "I'm with You" was released on March 31, 2003. The song debuted and peaked at number seven 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 number 58. It debuted at number six and peaked at number five 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 number 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, whilst her band members play the song alone in the streets. Showing her originally at a party, the video also sees Lavigne pushing a guy when he tries to get with her straight after making out with another woman. 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 music video was originally meant to end with Lavigne walking out of the club to her band mates, who then greet her and walk off together into the distance, but this ending was removed during post-production, ending the video with her leaving alone. An alternative version of the video leaked online to the internet, comprising alternate shots, slightly longer sequences and featuring the originally filmed ending.