The development is the latest in a long-running case that has gripped the public imagination after the death of an artist whose spectacular career was cut short at the age of just 25.
Duane “Keffe D” Davis was indicted by a grand jury in Nevada, prosecutor Marc DiGiacomo told a court.
“The presumption is great that he is responsible for the murder of Tupac Shakur, and he will be found guilty of murder with the use of a deadly weapon,” he said.
Shakur, the best-selling hip-hop artist behind hits such as “California Love,” was gunned down in a drive-by shooting in Las Vegas.
Shakur had a brief but stratospheric career, rapidly rising from backup dancer to self-styled gangsta rapper and one of the most influential figures in hip-hop, selling 75 million records.
He became a key figure in a vaunted rivalry, egged on by promoters, between East Coast and West Coast hip-hop.
Though born in New York, Shakur moved as a teenager with his family to California, becoming one of the most identifiable figures in the West Coast scene.
The circumstances of Shakur’s death in September 1996 remain murky, and theories have long abounded.
Shakur’s murder was followed six months later by the gunning down of his rival, East Coast rapper Christopher “The Notorious BIG” Wallace.
Many believe they were slain as part of a rivalry between their music labels, LA-based Death Row and New York’s Bad Boy Entertainment.
But some music historians say the coastal rift was exaggerated for commercial reasons.
Shakur — whose mother Afeni was active in the Black Panther movement and named him after Tupac Amaru, a revolutionary Inca chief — used his lyrics to highlight issues facing Black Americans, from police brutality to mass incarceration.