Nearly 20,000 people have signed a petition on Change.org calling on ITV to axe a storyline that involves a disability-selective abortion.
The plot revolves around Laurel, portrayed by Charlotte Bellamy, and her partner Jai, played by Chris Bisson, who choose to abort their unborn baby after being told that it might have Down's syndrome.
The Change.org petition was started by Rachel Mewes, whose 3-year-old daughter has Down's syndrome.
She accused ITV of being "irresponsible" and "ignorant" in "promoting" the abortion of babies with Down's syndrome.
She called the storyline "a perpetuation of the embedded prejudice towards people with Down's Syndrome that is a huge problem in our culture".
"It has shaken me to the core that a popular TV show watched by millions has sought to perpetuate the antiquated stereotyping, embedded and, often unconscious, prejudice combined with misleading information about Down's Syndrome that is endemic in our society," she said.
"Combined with that, we live in a country that has an NHS that does not have a care pathway for women expecting a child with Down's Syndrome."
Actress Sally Phillips, whose son has Down's syndrome, said on Twitter that the storyline was "on the wrong side of history".
Figures show an increase in disability-selective abortion in recent years, with 3,183 in England and Wales in 2019 - 656 of which followed a prenatal diagnosis of Down's syndrome.
Pro-life charity the Society for the Protection of Unborn Children (SPUC) accused Emmerdale of promoting eugenic abortion.
Michael Robinson, SPUC Director of Communications, said negative storylines were contributing to the stigma around Down's syndrome.
He said producers should have created a storyline that would challenge this stigma.
"There is huge amount of negativity and stigma surrounding Down's syndrome and people with Down's syndrome in the UK," he said.
"Storylines such as this contribute to this. When parents receive a Down's syndrome diagnosis for their child, it can be very scary.
"It is important that parents are met with support and encouragement, not filled with fear. This storyline in Emmerdale risks promoting eugenic abortion which is a barbaric form of discrimination against disabled people."
He continued: "TV soaps carry a huge responsibility as they have the ability to shape public opinion and attitude. It would be encouraging for these shows to depict pregnancy in a positive way.
"It would have been fantastic for Emmerdale to feature an empowering and inclusive storyline which valued this unborn baby and helped remove the stigma which surrounds disability."
"There'll be children with Down's Syndrome who'll have to go to the school playground after this has gone out."@Adam_Pearson has concerns about Emmerdale's abortion storyline - but @SusanJamson, whose daughter has Down's Syndrome, thinks it's good to raise awareness. Thoughts? pic.twitter.com/BfZ6Y0N9IX— Jeremy Vine On 5 (@JeremyVineOn5) November 11, 2020