The 49-year-old Knight, who could face life in prison if convicted, also denied two other charges over the incident in Los Angeles last week.
Shortly after entering his plea, Knight was taken to the hospital for an undisclosed medical problem, officials said.
Knight was ordered to return to court next Monday for a bail review hearing, after his initial USD 2 million bail was revoked because he was deemed a flight risk and could intimidate witnesses.
The apparent argument began on the set of "Straight Outta Compton," a movie about pioneering rap group NWA. Knight was arrested after being interviewed by homicide detectives within hours of the incident.
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One of the victims, 55-year-old actor Terry Carter, was declared dead at the hospital. The second man, 51-year-old Cle Stone, survived but no details on his condition were released.
Knight's lawyer said last week that the rapper was attacked by a number of men and had accidentally run over the victims while trying to escape, according to the LA Times.
"Mr Knight was attacked by a group of men while he was in his vehicle. They were beating him, threatening to kill him and attempting to drag him outside of the vehicle," attorney James Blatt told the LA Times.
The LA County Sheriff's department had said yesterday his bail was revoked because he was a possible flight risk, also citing "possible witness intimidation issues and a criminal past" as factors.
Knight co-founded Death Row along with hip-hop music king Dr Dre in the early 1990s.
The label launched stars such as Snoop Dogg and Tupac Shakur but collapsed in 1996 when Knight was jailed for violating a 1992 probation order by beating up a rival in Las Vegas.