Appleby began her acting career at the age of four, starting with advertising for various products such as Cheerios and M&M's. Her first advertisement was for Raisin Bran but it was never aired. She has had guest appearances on many television programs, most notably thirtysomething (1987), Doogie Howser, M.D. (1989), ER (1994), Baywatch (1989), Xena: Warrior Princess (1995), 7th Heaven (1996) and Beverly Hills 90210 (1990). For Roswell, she tried out for the roles of both Isabel and Maria before landing the role of Liz Parker. On 7th Heaven, she played a gang member who hid weapons underneath her little brother's mattress.

Appleby was in Bon Jovi's music video for "It's My Life" with Will Estes. She was also featured in the 2004 music video for the song "I Don't Want To Be" by Gavin DeGraw, opposite Scott Mechlowicz. She also appeared in Sense Field's music video for "Save Yourself" which is part of the Roswell soundtrack and featured in the first season DVD boxset.

In 2006 she could be seen in a recurring role on the now canceled ABC drama Six Degrees as Anya, a young assistant in a relationship with a much older photographer. Later that year she was chosen to play Hildy Young in the new USA Network series To Love and Die that began airing in late December 2008. Shiri also participated in a short film called Carjacking directed by Dan Passman and co-starring Geoff Stults from 7th Heaven fame. In 2007, she was part of the movie What Love Is with Cuba Gooding Jr., Matthew Lillard and Anne Heche. She also participated in another short film, Love Like Wind, this one from Shaolin Film Productions. At the end the year, she appeared as Charlie Wilson's press secretary, aka Jailbait, in the film Charlie Wilson's War, which stars Tom Hanks and Julia Roberts. In 2008, Appleby got a recurring role on the final season of ER, playing an intern named Daria Wade.

• "ER" .... Dr. Daria Wade / ... (9 episodes, 1994-2009)
       - Love Is a Battlefield (2009) TV episode .... Dr. Daria Wade
       - Separation Anxiety (2009) TV episode .... Dr. Daria Wade
       - The High Holiday (2008) TV episode .... Dr. Daria Wade
       - Age of Innocence (2008) TV episode .... Dr. Daria Wade
       - Oh, Brother (2008) TV episode .... Dr. Daria Wade
        (4 more)
• "To Love and Die" .... Hildy / ... (2 episodes, 2008)
       - Episode #1.1 (2008) TV episode .... Hildy
       - Pilot (????) TV episode .... Hildy Young
• "Fear Itself" .... Tracy (1 episode, 2008)
       - Community (2008) TV episode .... Tracy
• "Welcome to the Captain" .... Heather (1 episode, 2008)
       - The Wrecking Crew (2008) TV episode .... Heather
• Charlie Wilson's War (2007) .... Jailbait - Charlie's Angels
• "Six Degrees" .... Anya (6 episodes, 2006-2007)
  ... aka 6° (USA: promotional title)
       - Get a Room (2007) TV episode .... Anya
       - Slings and Arrows (2007) TV episode .... Anya
       - What You Wish For (2006) TV episode .... Anya
       - Masquerade (2006) TV episode .... Anya
       - The Puncher (2006) TV episode .... Anya
        (1 more)
• What Love Is (2007) .... Debbie
• The Killing Floor (2007) .... Rebecca Fay
• Love Like Wind (2007) .... The ghost
• Carjacking (2006) .... Cary
• Thrill of the Kill (2006) (TV) .... Kelly Holden
• I'm Reed Fish (2006) .... Jill Cavanaugh
• I-See-You.Com (2006) .... Randi Sommers
• Pizza My Heart (2005) (TV) .... Gina Prestolani
• Havoc (2005) .... Amanda