The guest spot will first be featured in a March episode of E! Entertainment Television's series, "Kourtney and Kim Take New York," debuting this January.
Kardashian will appear on "One Life to Live" in scenes with Cristian Vega, played by David Fumero, and Blair Cramer, played by Kassie DePaiva.
"I grew up watching 'One Life to Live,'" Kardashian said in a statement. "I hear I get into some trouble, and I am looking forward to it. This may be my acting debut but the Kardashians know a thing or two about drama."
"We are excited to welcome Kourtney to the show," added Executive Producer Frank Valentini. "We also look forward to the opportunity for this unique collaboration between the two shows. While Kourtney and Kim take on New York, we are thrilled to have 'One Live to Live' take on Kourtney."