"I have made the very difficult decision to not return to Batwoman next season," Rose said in a statement.
"This was not a decision I made lightly as I have the utmost respect for the cast, crew and everyone involved with the show in both Vancouver and in Los Angeles.
"Thank you to everyone who made season one a success – I am truly grateful," she added.
At this stage it's unclear why she quit the role, however there was severe backlash when Rose's casting was announced two years ago, which forced the actress to turn her comments off on Instagram for a period of time.
The hashtag #RecastBatwoman began trending on Twitter shortly after the announcement, with the campaign based on the idea that her sexuality was not technically "gay" because she self-identifies as gender fluid.
"Where on earth did 'Ruby is not a lesbian therefore she can't be batwoman' come from — has to be the funniest most ridiculous thing I've ever read," she posted on Instagram at the time.
"I came out at 12? And have for the past 5 years had to deal with 'she's too gay' how do y'all flip it like that?"
She finished saying the controversy had been a "rollercoaster" she needed a break from social media, adding: "If you need me, I'll be on my Bat Phone."
Last September, Rose revealed she had undergone emergency surgery after herniating two discs performing stunts on the series, leaving her in "chronic pain". She said she almost severed her spinal cord.
Warner Bros has vowed to recast a LGBTQ actress for the second season.
"(We) thank Ruby for her contributions to the success of our first season and wish her all the best," a statement said.
"The studio and network are firmly committed to Batwoman's second season and long-term future, and we – along with the show's talented creative team – look forward to sharing its new direction, including the casting of a new lead actress and member of the LGBTQ community, in the coming months."