Lionel Messi's 80th Champions League goal - leaving him eight behind Real Madrid's Cristiano Ronaldo - was cancelled out by Javier Hernandez as the holders, already assured of top spot, dropped points in Group E for the second time in a 1-1 draw.
Barcelona, having already clinched first in Group E, had nothing on the line in Wednesday's contest at Bayer Leverkusen, who needed a win to advance, reports Efe.
Messi opened the scoring for Barcelona and Javier "Chicharito" Hernandez equalised for Bayer, but the home side couldn't get the second goal they needed to win.
In London, Jose Mourinho's Chelsea side beat Porto 2-0 on Wednesday to win Champions League Group G and dispatch the Portuguese club to the Europa League.
The successful but mercurial coach and the World Cup-winning Spanish keeper famously butted heads during Mourinho's tenure at the helm of Real Madrid, where Casillas won a raft of titles over 16 seasons before leaving in July for Porto.
Porto prevailed 2-1 in the first leg, but Chelsea dominated Wednesday's contest at Stamford Bridge ground in London.
Diego Costa led Chelsea, fighting for every ball and picking up a yellow card as well as setting up the first goal for the home side.
Casillas stopped the shot by his Spanish international teammate, but Porto's Ivan Marcano put the ball in the net for an own goal. Willian got the insurance goal in the second half to give Chelsea the top spot in Group G and send Porto to the Europa League.
The group's second Round of 16 berth goes to Dynamo Kiev, 1-0 winners Wednesday over a hapless Maccabi Tel-Aviv.
In Group F, Bayern Munich, already assured of first place, topped Dinamo Zagreb as Arsenal posted an impressive 3-0 away victory over Olympiakos to grab the second spot and extend their streak of consecutive appearances in the Champions knockout stage to 16 years.
Olivier Giroud scored all three goals for the Gunners, with the last coming on a penalty, consigning Olympiakos to the Europa League.
AS Roma finished second in the group, despite looking ragged in a 0-0 draw with BATE Borisov.
Zenit St. Petersburg, who entered Wednesday's away match against Gent with a lock on first place in Group H, lost 2-1 after conceding a goal in the 78th minute.
The result sends Champions League newcomer Gent to the Round of 16, while Valencia is Europa League-bound after a dispiriting 2-0 loss to Olympique Lyon.
