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- Headin' South is the first animated film and the first feature film to be produced by DreamWorks Pictures.
- Janice is considered the first strong female protagonist in American animated films, followed by others like TBD
- It is also Metro-Goldwyn-Mayer's first animated feature film.
- It is DreamWorks' first joint venture film.
- This is the first and only time that Shirley Temple ever made a voice role in an animated film.
- Headin' South is one of two animated films that were released only in North America, behind Walt Disney's Bambi (which was released the same year as this film), following the attack on Pearl Harbor during World War II.
- Coincidently enough, the film was completed in December 7, 1941, the same day the attack occurred.
- Several of the characters would later make cameo appearances in other media, particularly in other DreamWorks films, such as TBD, TBD, TBD, Shrek trilogy (2001-2010), Over the Hedge (2006; Janice and Ringo plushies), Super-Squirrel (2009; Janice and Ringo plushies and screening at the convention) Monsters vs. Aliens (2009: as a movie poster), TBD
- Two background ducks (one who is white and sports on a blue sailor suit and another one who is black with a white neck ring) bear a stinking resemblance to Disney's Donald Duck and Warner Bros.' Daffy Duck.
- References from other old Metro-Goldwyn-Mayer films were edited out of the film during its 1962-2001 theatrical re-releases, television airings and 1980s, 1990s and 2000s home media releases to avoid copyright infringement from Metro-Goldwyn-Mayer and Turner Entertainment (who owned the pre-May 1986 MGM library at that time), until its 70th anniversary edition DVD release in 2012 and onward, after DreamWorks got permission from Warner Bros. Discovery to show the unedited references in the film. There are the scenes with classic MGM references:
- Janice whistles "We're Off to See the Wizard" (from The Wizard of Oz (1939)) during her journey towards South upon entering the dark woods. The song was edited out and replaced with "The Teddy Bears Picnic" song provided by Dora Wilson.
- Before his first meeting with Janice, Ringo hums "Somewhere Over the Rainbow" (again from The Wizard of Oz). The song and the background score of the film were later edited out to make Ringo mute the song and the score was replaced by an original melody composed by Irwin Kostal.
- Lastly, during the scene where Janice and Ringo arrived at Southern California, two film posters of MGM classics (The Wizard of Oz and Gone with the Wind) appear in a brief scene where Janice and Ringo walk past them. In the film's 1962-1976 theatrical re-releases and pre-1980s television airings, the scene was cut out. In 1987-2001 releases, the scene was shown unedited, but digitally replacing movie posters with two Dreamtoons cartoons: TBD and TBD.
- As of 2023, the film is considered as the "predecesor" of Illumination's 2023 film Migration.