The 25-year-old Mele, a convicted sex offender, entered a plea during a brief court appearance in Orange County Court in Goshen.
An Orange County grand jury handed up an indictment last week against Mele, who was last seen with Garza early on Dec. 3, 2008, leaving a Chelsea nightclub.
Mele was identified almost immediately as a person of interest in the disappearance.
For two years, Mele refused to talk to investigators. He wouldn't answer questions about the disappearance of Garza, a young woman who came to New York City with show-business dreams. Garza had moved to New York from Texas five months before she ran into Mele, never to be seen again.
Garza's remains were found last spring in Pennsylvania.
Mele faces 25 years to life in prison if he's convicted of murder.
Mele, wearing a green jail jumpsuit, his hands cuffed in front of him and shackled to his waist, entered the plea through his attorney, John Ingrassia, who declined to comment afterward.
"He's continuing to exercise his right to remain silent," Orange County District Attorney Frank Phillips said outside court after he was asked whether Mele was uncooperative.
Mele is already serving time for violating his parole as a sex offender, but that sentence formally ends on Dec. 24.
Judge Nicholas De Rosa said Mele's lawyer could make a written bail application in the new case; Phillips said later that his office would oppose any such attempt. "In any murder case, there's always a flight risk," the prosecutor said, and "25 to life is a great inducement."
Mele had several sex-offense convictions in New York, most involving approaching women while masturbating, and he was wanted in New Jersey for similar crimes. He was denied release in March by a board that cited his "history of sexually deviant behavior."
Mele refused to talk about Garza as he became the focus of the investigation. He was quickly locked up on a parole violation, and a body check revealed scratches and a possible bite mark on him.
Mele hid carpet pieces, a car mat and Garza's body in an effort to keep them from becoming trial evidence, Phillips has said.
At Mele's apartment, police found patches of carpet that had been cut away. They searched his vehicle and carried away bags of evidence for testing. But there was no sign of Garza.
As many as 200 firefighters, police officers and volunteers spent days searching in Orange and Sullivan counties in upstate New York. Officers looked through Mele's apartment complex, the woods and fields around it, septic systems and trash bins, and nearby roads. Divers went under the ice covering a lake.
Garza's brothers, Ivan and Nicolas, came east from Texas and posted "missing" signs with their sister's picture. When the search reached the one-month and one-year marks, they held vigils for her in Manhattan.
Hope that Garza would be found alive gradually evaporated.
On April 11, 2010, a group of ATV riders found what police described as "an intact skeleton" in Mount Cobb, Pa., several miles outside of Scranton. Police said a watch that Garza was wearing when she disappeared was found on the remains and DNA tests confirmed the identity.
The cause of her death was not made public.
De Rosa set Mele's next court appearance for March 7, 2011.
(Information from The Associated Press was used in this report.)