Porto closed the gap at the top to one point following their 1-0 success over Vitoria Guimaraes on Friday, thanks to a goal from Yacine Brahimi.
However, Benfica made sure they stayed on track for a record-extending 34th domestic title with a ruthless display against strugglers Setubal.
Champions Benfica are on 53 points from 21 games while Setubal are in danger of being dragged into a relegation battle as they are only three points above third-from-bottom Arouca.
Four days after Benfica beat Setubal 3-0 to reach the Portuguese League Cup final, the league leaders subjected their rivals to another drubbing by the same scoreline.
A ninth minute goal from defender Jardel set them on the path to victory, with Lima adding two more in the 40th and 71st minutes.
Third placed Sporting lost ground on the leaders after 1-1 draw at Belenenses.
(Reporting by Simon Curtis, editing by Pritha Sarkar)
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