The Saints, coached by former Barcelona and Spain striker Juan Antonio Pizzi, topped the Inicial championship with 33 points from 19 matches, two more than Velez, Newell's and Lanus.
It was San Lorenzo's 12th league title in the professional era and first since the 2007 Clausura championship.
"We were one of the teams that most tried to play (good football) and among those that did it best," said forward Ignacio Piatti, San Lorenzo's top scorer with eight goals.
"We deserved this, the Cup and all," he added referring to qualifying for next year's Libertadores Cup, South America's top club tournament.
"We won a very even tournament of a very high standard... leaving the two biggest clubs with the two top coaches by the wayside," said Pizzi, referring to Boca Juniors and River Plate.
San Lorenzo made hard work of getting over the line with two scoreless draws in their last two matches. A home win over Estudiantes two weeks ago would have settled the championship.
On Sunday, they were indebted to goalkeeper Sebastian Torrico for two brilliant saves that kept them in the match at Velez's Fortin ground.
In an exciting clash at the Marcelo Bielsa stadium, Newell's looked set to take the title race to a playoff against San Lorenzo on Wednesday before substitute Jorge Pereyra Diaz headed Lanus's equaliser 15 minutes from time.
Newell's, who won the Final championship under Gerardo Martino last season, failed to win any of their last eight matches and garnered only five points during the slump.
They managed to take the race down to the wire because of the inconsistency of their challengers.
All four goals came in an absorbing second half on Sunday, with good football from both Newell's and Lanus, who won the regional Copa Sudamericana on Wednesday.
Midfielder Pablo Perez put the home side ahead in the 54th minute when he found a small gap between goalkeeper Agustin Marchesin and the post.
A minute later, Lanus centre back Paolo Goltz equalised with a header from a free kick, though video replays suggested he had strayed into an offside position.
Newell's went ahead again with an own goal from defender Carlos Izquierdoz. Milton Casco's angled shot looked off target but the ball hit Izquierdoz full in the chest and went in.
There was time for more drama and Pereyra Diaz headed home at the near post to make it 2-2, sparking celebrations by San Lorenzo fans in the capital as the news came through.