On a night of standout individual performances Wednesday, Schalke goalkeeper Timo Hildebrand had a game he'll want to forget. His failed clearance led to Eto'o's opening goal in Chelsea's 3-0 win, which put Jose Mourinho's side atop Group E.
Barcelona made it to the last 16 with a 3-1 win over visiting AC Milan, which now has to battle with Ajax and Celtic for second place in Group H.
Atletico Madrid ensured it will progress with a convincing 4-0 victory over Austria Vienna.
Barcelona and Atletico joined title holder Bayern Munich and Manchester City, which reached the knockout stage on Tuesday.
Napoli remained level atop Group F with Arsenal following a 3-2 win that eliminated Marseille. Aaron Ramsey scored the winner as Arsenal won 1-0 at last season's runner-up Borussia Dortmund.
In Barcelona, Messi scored a 30th-minute penalty for his first goal at the Camp Nou Stadium since Sept. 24 before Sergio Busquets doubled the host's lead with an angled header nine minutes later.
An own goal by Barcelona defender Gerard Pique reduced the margin to 2-1, but Messi sealed the win after finishing a combination with Cesc Fabregas in the 83rd.
Barcelona clinched a place in the second round thanks to Ajax's 1-0 victory over Celtic.
Barcelona leads Group H with 10 points, Milan has five points, Ajax has four and Celtic is bottom with three.
Messi has struggled following an injury-riddled October, going four league games without a goal for the first time since the 2010/11 season.
And while the Argentina forward still does not appear to be 100 per cent fit, his finishing touch in front of goal remains unflinching.
"Leo played a phenomenal game, he was sharp, showed quickness and was better one-on-one," Barcelona coach Gerardo Martino said.
In Naples, Higuain's finishing form was also on display. He used one touch for each of his goals, which included a 75th-minute winner following a cross from rapidly developing Belgium forward Dries Mertens.
"He made the difference," Napoli coach Rafa Benitez said. "It's very important for us to know that he can be so decisive."
In London, Eto'o scored twice in an impressive goalscoring comeback in the competition. His second goal came nine minutes after halftime, with Willian slipping the ball through and Eto'o clipping a shot past Hildebrand.
Eto'o scored his first goal in the Champions League for Mallorca in 2001, against Schalke. He went on to score goals for Barcelona and Inter Milan in Europe's top flight.
However, Eto'o didn't play in the Champions League the past two seasons with Russian club Anzhi Makhachkala.
"He was for two years playing without big motivations and when you play without big motivations ... you lose condition, you lose sharpness and you even lose appetite," Mourinho said.
After missing out on the knockout phase last season, Chelsea needs just one point from the last two Group E games to advance.
Chelsea is three points clear of Schalke, and four clear of Steaua Bucharest, which drew 1-1 at Basel.
In Group G, Atletico got goals from Miranda, Raul Garcia, Filipe Luis and Diego Costa for a club-record fourth straight victory in the Champions League.
Atletico leads with 12 points, seven clear of Zenit St. Petersburg and eight clear of Porto. Zenit and Porto played to a 1-1 draw.