As the match approached the half-hour mark, San Lorenzo doubled the advantage and the goal again came from a Romagnoli free-kick which right-back Emmanuel Mas sent home to double their tally.
Before the break, home striker Ignacio Piatti had a clear chance to extend the scoring but he failed when in a one-on-one with Bolivar goalkeeper Romel Quinonez.
Midfielder Juan Mercier clinched the third goal of the night with a cross after he took advantage of some poor defending.
While left-back Julio Buffarini put them further ahead after 73 minutes as he connected with a superb shot from outside the box before Mas headed home another free-kick to seal the win with five minutes to go.
"It was what we were looking for, we wanted to make a good difference at home ahead of the match in Bolivia. Today we did an excellent job and for that we won with a huge score," said man of the match Matos.
In Tuesday's other semifinal, Paraguay's Nacional edged closer to their first ever appearance in the Copa Libertadores finals with a 2-0 win over Defensor Sporting of Uruguay.
After the World Cup break, the Copa Libertadores resumed with a convincing win by the surprise semi-finalists, giving them a decent cushion ahead of the second leg in Montevideo next Tuesday.
Brian Montenegro opened the scoring in the 34th minute, beating Defensor goalkeeper Martin Campana with a left-footed strike after being teed up by Julian Benitez.
Derlis Orue then volleyed home the second from a corner kick in the 70th minute.
Montenegro, who signed for the club from Libertad only days before the match, told Fox Sports: "I'm very happy to get this goal on my debut and it gave me and the team confidence for the rest of the game.
"Now we'll do our best in Uruguay. It is a good score but they are strong at home. We must hold the lead and see if we can score one more."