Before breaking into show business, Harrison was a cheerleader from 1978–1980 for the Los Angeles Rams. In 1980, Harrison graduated with an education degree from USC. In the same year, she won the title Sweetheart of Sigma Chi. It was while studying at USC that Jenilee first met acting coach Joyce Selznick. Selznick gave her a lot of handy tips on how to polish her acting skills.

Harrison joined the cast of ABC’s Three’s Company in 1980. She entered the show as a replacement for Suzanne Somers who played the sitcom’s “ditzy blonde” Chrissy Snow. Somers left the show just after the show’s fifth season had begun. Harrison was cast as Somers’ replacement. Harrison’s character, Cindy Snow, was created to be Chrissy Snow’s cousin. Unlike Chrissy, Cindy was not a “dumb blonde”; instead, she was an extremely clumsy farm girl. The character of Cindy was similar enough to Chrissy, however, that producers could use scripts already written with the Chrissy character in mind. Harrison debuted on Three’s Company in the episode entitled “Chrissy’s Cousin” (season five, episode seven). She enters as Jack and Janet’s new roommate after Chrissy’s departure. Cindy proves she is a klutz right away by knocking Jack down. Her constant “accidents” (mainly with Jack) added to the show’s gags of characters being clumsy. Though she had replaced Somers, Harrison was not given opening-credits billing, and instead Somers still obtained opening billing (as a part of finishing off her contract). Harrison was end-credits billed, as a guest star.

Beginning in 1984, Harrison portrayed the recurring character Jamie Ewing Barnes in the drama Dallas. She played the role until 1986. Her character was actually killed off twice, first when she starts the car belonging to her brother, Jack Ewing, in the episode “Blast from the Past” and it explodes, killing her. After the entire ninth season was explained away as a dream, Harrison returned for her character to die again. Early in 1987, Jamie was killed in a mountain-climbing accident.

In 1984, Harrison played a reluctant prostitute in the movie Tank alongside James Garner and C. Thomas Howell.

In 1985, she appeared on Super Password with Dick Gautier, appearing again in 1986, this time with Marty Cohen, Michael Young, and Bruce Baum, and Dallas star Ken Kercheval in 1987 with Bert Convy. Also, in 1985, she made a brief appearance as a waitress in Loverboy’s music video “Lovin’ Every Minute Of It”.

In 1993, Harrison married Dr. Bruce Oppenheim, a prominent Los Angeles-area chiropractor, who is the ex-husband of actress Cybill Shepherd. She has two stepchildren from her husband’s previous marriage to Shepherd: Molly Ariel Shepherd-Oppenheim and Cyrus Zachariah Shepherd-Oppenheim.

Between 1996 and 2005 Harrison began appearing in a couple of “As Seen on TV” infomercials like the AB Flex, the Sobakawa Pillow and the Ultimate Chopper with Chef Tony.

Harrison also guest-starred on That ’70s Show in 1999. In 1991, she starred in the movie Panga opposite Christopher Lee.