Fredy Guarin and Hulk scored to seal victory for unbeaten Porto, who moved 16 points ahead of their Lisbon rivals with just five games to go.
A howler by Benfica's Spanish keeper Roberto gifted Porto the lead on nine minutes when he fumbled a soft cross by Colombian midfielder Guarin and touched the ball into his own net.
Last season's champions Benfica levelled from the spot after Argentine defender Nicolas Otamendi fouled his compatriot Franco Jara and forward Javier Saviola converted the penalty in the 15th minute.
Porto went ahead again 10 minutes later, also from a penalty. Guarin sent fellow Colombian Radamel Falcao through and the striker was brought down by Roberto, with Brazilian forward Hulk firing in the from the spot.
Saviola threatened again five minutes after halftime with a turn and shot that keeper Helton had to block away for a corner.
Falcao should have added Porto's third on 56 minutes but after stealing the ball from Sidnei, who was Benfica's last man in defence, he sent his shot just wide.
Porto were reduced to 10 men when Otamendi was sent off for a second booking.
Either side could have scored in a hectic finale, with Eduardo Salvio hitting the Porto post and former Benfica player Cristian Rodriguez forcing Roberto to make a fine save in stoppage time.
He showed, like his former boss, the ability to build a defensively solid and well-organised side. Also like Mourinho, he is not shy when it comes to making controversial remarks to protect his team.
"We battled throughout to show we are the best team even though the press insisted on believing otherwise... but we proved it in this most difficult of venues," he told reporters.
"We showed who plays the best football. This was constantly ignored, on a daily basis by everyone so our cry of revolt against that helped us, with merit due to the players, to win the title," he added. Porto have dominated the season, leading throughout and dropping only four points in 25 matches. Benfica started the season dismally and though they have improved, they never came close to catching their rivals.
The northern club would become only the second team in the league's history to complete a season undefeated if they avoid losing any of their remaining five games.