Duane "Keffe D" Davis, 63, is charged in Nevada's Clark County with a single count of murder using a deadly weapon.
He has pleaded not guilty.
Davis is accused of leading a group of men to kill Shakur, 25, who was one of rap's most commercially successful and influential artists, in a drive-by shooting near the Las Vegas Strip.
"You will learn that when the opportunity presented itself for retribution, Duane Davis made sure that the shooters were armed and ready to execute their plan. And remarkably, you will learn that from Duane Davis himself," prosecutor Binu Palal told the jurors in a downtown Las Vegas courthouse, referring to recent public statements by Davis that revived the long-dormant case.
Defence lawyer Michael Sandt said that after 30 years, investigators still have very little evidence to prove their case.
"At the end of the day you have to ask yourself, is what they are saying truth or fiction?" Sandt told the jury.
Shakur's killing heightened the image of violence permeating hip-hop culture and its lyrics during "gangsta" rap's golden age, stoking that era's east coast-west coast rap feud.
Police said after the 2023 arrest of Davis that he was a longtime suspect in the killing but that investigators had lacked sufficient admissible evidence to charge him until he began implicating himself in a series of public statements.
The trial before judge Carli Kierny is expected to last up to six weeks.
The jury was selected last week.
The trial 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.
Authorities have described Davis as the "shot caller" of a hurried plot to avenge the beating of his nephew by Shakur and members of the rapper's entourage inside the MGM Grand casino in Las Vegas the night of September 7, 1996.
The violence at the casino 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.
They were in Las Vegas to see a world heavyweight title boxing match between Mike Tyson and Bruce Seldon.
Davis allegedly obtained the murder weapon and handed it off to two other men in the rear seat 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.
Knight, who had been driving, suffered a minor wound from a bullet fragment that grazed his head.
The murder investigation grew cold for years but police said statements Davis made in 2018 to various media outlets about his involvement in the shooting reinvigorated the case.
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.
But neither Davis, in his account, nor authorities have said who fired the gun at Shakur.
The three other men in the Cadillac with Davis have all since died.
Under Nevada law, Davis can be charged with murder if he took part in the crime without pulling the trigger.
