US captain Pulisic curled in a superb early goal before teeing up a second for striker Folarin Balogun just before half-time at the AT&T Stadium in Arlington, Texas.
“We came out flying with a lot of intensity,” Pulisic said.
“Obviously an early goal helped us a lot, but all around a pretty dominant performance.”
US coach Gregg Berhalter had warned his team against complacency against a Bolivia side who had won only one game in nine previous editions of the Copa America since 1999.
Pulisic was clearly in no mood to let the South Americans improve that record, firing the hosts into the lead after only three minutes.
Receiving the ball from a corner on the left, Pulisic darted towards the edge of the area and whipped a rasping shot goalwards.
Bolivia goalkeeper Guillermo Viscarra got a hand to it but could not stop the ball flying into the roof of the net.
Despite that early breakthrough the US struggled to convert their dominance into chances and were frustrated by a combative Bolivian team who had three players booked in the first 31 minutes.
Leonel Justiniano, Gabriel Villamil and Luis Haquin were all shown yellow cards in an indisciplined start by Bolivia.
The US doubled their lead in the 44th minute and once again Pulisic was heavily involved.
Picking up the ball near halfway, the AC Milan forward accelerated towards the penalty area and squared to Balogun, who took a touch to drag defender Jesus Sagredo wide before drilling a low shot into the bottom corner.
The superior movement of the US forward line continued to cause problems after the restart.
Balogun just failed to get a toe on a low shot by Tim Weah in the 50th minute and had the ball in the net moments later but was adjudged marginally offside.
Pulisic then drew a fine save from Viscarra in the 60th minute after weaving into the penalty area and unleashing a ferocious shot.
Substitute Ricardo Pepi should have made it 3-0 in the 65th minute, moments after coming on for Gio Reyna, but saw his shot from an Antonee Robinson cross roll wide.
Pepi was then denied a goal in the 90th minute after a desperate double save by Viscarra.
Relentless Uruguay
Marcelo Bielsa’s Uruguay began in trademark fashion, swarming opponents Panama and pressing relentlessly.
Maximiliano Araujo put Uruguay ahead in the 16th minute with a beautifully executed left-foot shot into the top corner.
Panama keeper Orlando Mosquera had to be at his best to deal with the wave of attacks, parrying a fiere Nunez blast and then producing an outstanding save to keep out a header from Giorgian de Arrascaeta.
Mosquera’s reflexes served him well again in the 29th minute when he denied Nunez from close range, the Liverpool striker having connected on a low cross from Federico Valverde.
It was a very different story after the break, though, with Uruguay looking a little tired and Panama enjoying some sustained pressure.
But Bielsa’s side gave themselves breathing space when Nunez doubled their lead in the 85th minute, showing his superb technique to volley home a half-clearance from inside the box.
Matias Vina’s perfectly timed header from a Nicolas de la Cruz free-kick put an end to the contest, although Panama received some reward in the final minutes with Michael Amir Murillo finishing off a swift break.
“In the first half we were better. In the second half they controlled the game for the first 15 or 20 minutes,” Nunez said.
“We suffered a bit, but with the second goal we improved again and ended up playing well,” said the striker.
“We missed a lot of chances, a lot of plays that ended badly. But you learn from mistakes and we never gave up,” he added.
© Agence France-Presse
Photo: Twitter @Mobyhaque1