The actress, who played Detective Stella Bonasera, opted not to accept a new contract for the series in favour of moving on to other projects, reports Entertainment Weekly.
“I made some amazing and lifelong friendships during my six seasons on CSI: NY, and I will treasure them forever," she said in a statement.
CBS also expressed its disappointment at Kanakaredes's decision, saying: "We hoped Melina would return to CSI: NY for another season, but we respect her decision to move on.
"Her amazing talent and invaluable contribution to the success of the series are greatly appreciated and will not be forgotten. She will forever remain a friend to the network and studio and we wish her the very best."
Sela Ward is in talks with the network to replace Kanakaredes next season.