Although the show is set in Seattle, Washington, it was actually filmed in the Vancouver, British Columbia area.

The series finale ended with several cliffhangers that were never resolved on air, but were eventually explained in a special feature included on the third season DVD.

Kyle XY was ABC Family's highest-rated original series from June 2006 to July 2008, until this record was surpassed by the premiere of The Secret Life of the American Teenager, which drew 2.8 million viewers.

The show's third-season premiere drew only 1.5 million viewers, a 33 percent drop from the second-season opener, with most other ABC Family shows outperforming it by that point.

During its first season, Kyle XY featured an online alternate reality game inviting players to help solve the mystery of Kyle's true identity, hosted via a website for the fictional company The Mada Corporation created by ABC Family and Touchstone; the project was discontinued during the second season.

Two tie-in novels based on the series, both written by S. G. Wilkins, were published: Kyle XY: Nowhere to Hide, about Kyle's first Halloween, and Kyle XY: Under the Radar, about a school student president election featuring Kyle as a candidate.

The show's opening theme and most of its score and cues were composed by Michael Suby, though none of his musical work ended up appearing on the official soundtrack album released in 2007.