Saul Niguez and Luciano Vietto put Diego Simeone's side 2-0 up inside an hour before Kostantinos Mitroglou replied to give hope to Benfica with the Portuguese needing a draw to claim first place in the table.
Both teams had already qualified but victory meant Atletico finished with 13 points from six games, three ahead of Tuesday's opponents. Galatasaray drew 1-1 with Astana of Kazakhstan to end up in third place and progress to the Europa League.
Atletico defender Diego Godin had a goal disallowed while Benfica goalkeeper Julio Cesar also had to palm away shots by Niguez and Gabi.
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The visitors deservedly went ahead with a well-worked goal in the 33rd minute as Antoine Griezmann fed Vietto down the right and the Argentine produced a clever reverse pass for Niguez to sidefoot the ball into the net.
Benfica brought on Mitroglou at halftime and the Greek made an immediate impact, working an opening in the penalty area and sending a low shot into the side-netting within a minute of the restart.
Atletico struck again when Vietto nipped in at the near post to deflect Yannick Carrasco's low cross between Julio Cesar and his near post in the 55th minute.
Mitroglou reduced the arrears, and brought the hosts to life, with a quarter of an hour to play as he controlled Raul Jimenez's pass and beat Jan Oblak with a shot on the turn.
Benfica failed to create many more clear-cut openings and only once looked like equalising when a cross found Jimenez who headed wide from six metres.
(Writing by Brian Homewood; Editing by Tony Jimenez)
