Title holders Manchester City and RB Leipzig qualified for the Champions League last 16 with victories on Tuesday while Barcelona failed to advance prematurely as well owing to a 1-0 defeat against Shakhtar Donetsk.
City beat Swiss side Young Boys 3-0 from Erling Haaland's brace and Phil Foden to make it four wins out of four in Group G, from which Leipzig also progressed by prevailing 2-1 at Red Star Belgrade.
Barca failed to maintain their perfect record in Group H, and did not even manage a draw which would have also seen them into the knock-outs for the first time in three years, losing instead against Shakhtar from Danylo Sikan's first-half header.
That threw the group wide open again, as Porto drew level with Barca on nine points courtesy of a 2-0 against 10-man eliminated Royal Antwerp from a penalty by Evanilson and veteran captain Pepe. Shakhtar are lurking three points back in third.
There is also still plenty to play for in Group F where the four teams are separated by three points.
Borussia Dortmund went top with seven points by beating Newcastle United 2-0, moving one ahead of Paris Saint-Germain who lost 2-1 at AC Milan who are another point back after their first win and goals, and one ahead of Newcastle.
Atletico Madrid stormed back into first place in tight Group E by thrashing 10-man Celtic 6-0, with Antoine Griezmann and Alvaro Morata getting a brace each against the eliminated Scots.
Atletico are one clear of Lazio who beat Feyenoord 1-0 from Ciro Immobile's 200th goal for the club which sent the Dutch down to third, but only two points off the top.
Matchday four is completed on Wednesday, with record winners Real Madrid and Bayern aiming to follow City and Leipzig into the knock-outs.
City were frustrated by Young Boys goalkeeper Anthony Racioppi early on but he was sent the wrong way by Haaland's 23rd minute penalty, and beaten again by Foden from a right angle on the stroke of half-time.
Haaling smashed a superb third into the far corner in the 51st, and Young Boys' Sandro Lauper was sent off shortly after, after also having conceded the first-half penalty, and having seen red on the weekend as well in the Swiss league.
"To qualify with two games to spare, that is what we wanted to do," City forward Jack Grealish told TNT Sport. "We love being with each other every day and playing with each other."
Leipzig had a dream start in Belgrade from Xavi Simons' eighth-minute drive into the top right corner.
Benjamin Sesko hit the left post for Leipzig after the break before Lois Openda fired the second into the near left corner in the 77th. But an own goal from Benjamin Henrichs four minutes later made the 2020 semi-finalists Leipzig sweat it out in the end.
"We won in the end and have advanced. It wasn't easy. We were a little sloppy in the second half," Leipzig midfielder Emil Forsberg told streaming portal DAZN.
In Hamburg, where Shakhtar are playing their home games this season owing to the war in Ukraine, Shakhtar contained Robert Lewandowski and his Barcelona team-mates well and only allowed them a few efforts from a distance which all went off target.
Sikan's looping 40th-minute header into the right corner off Giorgi Gocholeishvili's cross from the right made the difference, and Shakhtar had a late a second goal disallowed because teenager Newerton was narrowly offside before firing into the far corner.
"We leave this match feeling angry. Our play wasn't good enough. None of the things we planned came off, we're angry at ourselves. This is a clear setback," Barca coach Xavi Hernandez said.
In Group F, former Inter Milan player Milan Skriniar headed PSG ahead nine minutes into the game against AC Milan from point-blank range.
But Milan were level three minutes later from their first goal of the competition, an artistic overhead kick from Rafael Leao. French striker Olivier Giroud completed the turnround with a 50th-minute header to give Milan a first win and revive the knock-out hopes of the seven-time winners.
Dortmund's Germany striker Niklas Füllkrug opened the scoring in the 26th minute against Newcastle off Marcel Sabitzer for his first goal in the elite event.
Joelinton headed wide in the visitors' best chance early in the second half, before Julian Brandt wrapped up matters in the 79th.
"That was a very important step and a great reaction after the game on Saturday," Füllkrug told Prime Video, referring to Dortmund's 4-0 Bundesliga home defeat against Bayern Munich.
