- Went to Westminster High School in Atlanta, Georgia, with Brian Baumgartner, fellow cast member on The Office (2005).
- Plays the banjo and piano, and has played both in some of his TV and movie appearances. Wrote and sang "Stu's Song" in The Hangover (2009).
- Got food poisoning during the shooting of The Hangover Part II (2011) after eating street food in Bangkok. He actually filmed some scenes for the film while being severely sick.
- Plays bluegrass guitar and banjo in various bands.
- Was nicknamed "Chuck E. Cheese" when he was in school.
- Helms is an accomplished harmonica player as he demonstrated to Bear Grylls on the Adventure-Survival series, Running Wild (Season 2).
- Graduated from Oberlin College.
- Son of Pamela Ann (Parker), a school administrator, from Tennessee, and John A. Helms, a lawyer, insurance executive, and Navy veteran, from Alabama.
- Has done much voiceover work for companies such as Lycos, CDnow.com, Burger King, etc..
- He has English, as well as smaller amounts of Scots-Irish/Northern Irish, German, Dutch, and French, ancestry. He has deep Colonial American roots in Virginia, Maine, Vermont, and Connecticut, including descent from the real-life Griswold family (he played the fictional Rusty Griswold in Vacation (2015).
- Studied at the Upright Citizens Brigade Theater.
- Lived in New York City for 10 years.
- No effects were done for his characters missing tooth in The Hangover (2009). Helms never had an adult incisor grow so he simply took out his fake tooth in the scenes it wasn't there.
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