Duane "Keffe D" Davis, 63, is charged in Clark County, Nevada, with a single count of murder by use of a deadly weapon. He has pleaded not guilty.
Davis is accused of leading a group of men to kill Shakur, 25, one of rap's most commercially successful and influential artists, in a 1996 drive-by shooting near the Las Vegas Strip. He faces a potential life sentence without parole if convicted.
Jury selection could last several days. Around 75 potential jurors were summoned to court on Monday to be questioned about their ability to be fair and impartial.
Shakur's killing heightened the image of violence permeating hip-hop culture during "gangsta" rap's golden age, stoking an infamous East Coast-West Coast rap feud.
Police said after Davis' 2023 arrest that he was a long-time suspect in the killing but investigators lacked sufficient evidence to charge him until he began implicating himself in public statements.
The trial before Judge Carli Kierny is expected to run for up to five weeks in a downtown Las Vegas courthouse. It may feature testimony from Death Row Records co-founder Marion "Suge" Knight, a former rap mogul who was with Shakur the night he was slain and is now serving a 28-year prison sentence on an unrelated voluntary manslaughter conviction.
William Lesane, who said he was Shakur's cousin, told reporters outside the courtroom that the trial was the culmination of 30 years of grief and trauma for his family.
"Hopefully we'll find out some new information. And more importantly, the right person is charged and convicted for Tupac's murder," Lesane said.
Authorities have described Davis as the "shot caller" of a hurried plot to avenge the beating of his nephew by Shakur and members of his entourage inside the MGM Grand casino in Las Vegas the night of September 7, 1996.
The violence allegedly stemmed from hostility between two Los Angeles-area street gangs - the South Side Compton Crips, of which Davis was the self-described leader, and Mob Piru, which police say was associated with Knight and Death Row Records.
Davis allegedly obtained the murder weapon and handed it off to two other men in the rear of a white Cadillac as they rode around looking for Knight and Shakur's car following the brawl.
Shots were fired when Davis and the others caught up with Knight and Shakur's vehicle. Shakur was struck four times and died in a hospital six days later.
The murder investigation grew cold for nearly three decades, but police said the case was reinvigorated in 2018 by Davis' public statements about his role in the shooting.
Davis said in interviews and in his 2019 memoir, Compton Street Legend, that he was riding in the front passenger seat of the Cadillac and had handed the gun to one of the two men sitting behind him, according to police.
Neither Davis nor police have said who fired the gun at Shakur, and the three other men in the Cadillac with Davis have died.
