Stefan Radu opened his Serie A account in stunning fashion after 29 minutes, but not wanting to be outdone, Senad Lulic fired in an even better second five minutes later as Vladimir Petkovic's men moved to within five points of second-placed Napoli.
Pescara made a game of it in the second half, but were unable to find a route back into the contest as they remained in the bottom three, five points adrift of safety.
Lazio were quick to impose themselves on proceedings, not showing any signs of tiredness from their Europa League victory over Borussia Monchengladbach last Thursday.
Sergio Floccari turned and sent a shot just wide of Ivan Pelizzoli's post with their first attempt early on, but that effort was bettered by Radu, who scored his first league goal in his 119th game just before the half-hour.
It was certainly worth the wait too as he picked up the ball just outside the penalty area and curled in an unstoppable shot inside the near post.
Six minutes later, Lulic doubled Lazio's lead in similarly impressive style as he unleashed a thunderous shot from 25 yards which struck the underside of the crossbar on its way in.
The chances of Pescara recovering looked slim, but they battled hard after the break, ensuring Lazio had to keep their concentration high right to the end.
However, the best chances still fell to the home team with Floccari twice going close, although a further goal was not required to end their search for a win after a five-game wait.