Inter were joined in the next round by a host of clubs, among them 2008 winners Manchester United, for whom England striker Wayne Rooney marked his return to the starting line-up for the first time since October with a late penalty in a 1-0 win at Scottish champions Rangers.
Valencia's 6-1 humbling of Turkish whipping boys Bursaspor ensures they join United from that group and consigns Rangers to the Europa League.
Champions League debutants Tottenham Hotspur's dream campaign continued as they defeated hapless German side Werder Bremen 3-0 to leave them above Inter on head-to-head results.
Barcelona's bid to regain the trophy they won in 2009 remains on track as they reached the next stage with a convincing 3-0 win away at Panathinaikos thanks to a double from Pedro Rodriguez and one from Lionel Messi.
Danish side FC Copenhagen could have joined them and become the first side from their country to reach the knockout stages but they lost 1-0 at Rubin Kazan, leaving the runners-up spot still up for grabs -- the only qualifying place not to be resolved on Wednesday.
Esteban Cambiasso, a controversial omission from Argentina's World Cup squad, lifted the tension surrounding holders Inter and coach Benitez in the 55th minute at San Siro, though his goal was a fortunate one.
A Wesley Sneijder free-kick took a double deflection and fell kindly to the unmarked Cambiasso to swivel and fire home inside the post.
Cambiasso said he hoped the win could be a springboard for the club.
"In the changing room we never had any doubts we'd bounce back. We knew we were in a difficult moment but we hope this result can give us tranquility and once we're back to full strength, things can go much better," he said.
Spurs travel to Twente next month bidding to clinch first place in the group ahead of Inter, but one of their goalscorers Peter Crouch doesn't want the team to rest on its laurels.
"It's a great achievement but obviously we don't want to rest on that -- we want to go out and give a good account of ourselves in the next round," Crouch told Sky Sports.
"It's massive. Every big club wants to be in the Champions League, playing against the best teams in the world. We haven't looked out of place at all."
Schalke's disciplinarian coach Felix Magath has ridden a storm of criticism for a disastrous opening part of the season but he took delight in reaching the last 16 after a 3-0 win at home to Lyon.
"It's a nice feeling, because for weeks we have been written off, but now we will play in the knockout stages," said Magath.
Lyon slipped to second in Group B, but their superior head-to-record with Benfica means that they are assured of a place in the next round at the Portuguese champions' expense.
Rooney had an up-and-down game at Ibrox -- after weeks of largely negative headlines concerning his private life and his contract saga with the club -- but showed admirable nerve in tucking away the 87th-minute penalty that guaranteed United's place in the last 16.
United manager Sir Alex Ferguson praised Rooney for his coolness.
"It took courage for Wayne Rooney to take that penalty," said the Scot.
"It wasn't the easiest of nights for him as he missed a couple of chances. There's still a bit of rustiness to his game."
Valencia's win was never in doubt, with Roberto Soldado scoring a brace, but there was one consolation for the visitors in that they scored their first goal of the group phase through Argentinian midfielder Pablo Batalla.