Nelkin starred as Bonnie Sue Chisholm in four episodes of the CBS western miniseries The Chisholms (1979).
She became well known for her role in the horror film Halloween III: Season of the Witch (1982) as Ellie Grimbridge. Around the same time, Nelkin was scheduled to appear in the film Blade Runner as Mary, a sixth Nexus-6 replicant that escapes from "off-world" and comes to Earth, but budget cuts resulted in her part being cut from the film early in the period of principal photography. She had done a screen test for the role of Pris in Blade Runner as well. Nelkin's screen test appears on Disc 4 of the collector's edition DVD set. Nelkin has made guest appearances in several TV series, including CHiPs, The A-Team, Eight Is Enough, 1st & Ten and Hunter. She has also had significant roles in Serial and Up the Academy.
Her best-known TV role was on the soap opera Generations (1990) as Christy Russell.