Inter have a chance to become the first Italian side to ever beat Barcelona twice in a Champions League campaign when they meet at Camp Nou on Wednesday.
Meanwhile, Club Brugge are on the brink of their first trip to the knockout stages as they play Atletico Madrid.
Mohamed Salah can make history with one more Champions League goal for Liverpool on their trip to Scotland to take on Rangers, and Bayern Munich are one win away from their own record as they try to win an 11th consecutive group stage match.
Tottenham will look to break out of a scoring slump when they host Eintracht Frankfurt, while Porto and Bayer Leverkusen are battling it out in Group B.
With plenty of important matchups, Stats Perform has parsed through the data to preview the eight fixtures on Wednesday and shine a light on some of the more interesting angles.
Barcelona v Inter
Inter's 1-0 victory against Barcelona at San Siro last week was their first triumph over the Spanish giants since April 2010, with Barca collecting four wins and one draw since.
With another win, Inter can become the first Italian side to ever beat Barcelona twice in the same Champions League campaign, although they have lost all five of their away fixtures at Camp Nou – their most losses at any away venue in the competition.
In fact, Camp Nou has not been a happy hunting ground for Italian sides in general, with a 3-0 victory for Juventus in 2020 marking the country's only win at the venue in the last 17 tries (L13 D3).
It is not just Barcelona who have given Inter trouble on away days, with their last away win in the Champions League against a Spanish opponent coming back in 2004 against Valencia.
Working in Inter's favour is road warrior Lautaro Martinez, who has scored six of his seven Champions League goals away from home.
Tottenham v Eintracht Frankfurt
After banking four consecutive wins against Borussia Dortmund between 2017 and 2019, Tottenham are now winless in their past five Champions League fixtures against German sides (D1 L4).
On the other side, Eintracht have enjoyed success when travelling to England in European competition, winning both of their previous two attempts – against Arsenal in 2019, and West Ham in April this year – in the Europa League.
However, this is a clear step up from the Europa League, and after winning their first ever Champions League away game last month (1-0 at Marseille), Frankfurt will be looking to become the only German team to ever win their first two away fixtures in the competition.
The 0-0 draw between these two sides in Frankfurt a week ago was the second consecutive Champions League game where Tottenham have failed to score a goal – also losing 2-0 to Sporting. The last time they went three games in the competition without scoring was back in 2011.
Striker Harry Kane will be key, as he boasts the best minutes-per-goal figure – 20 goals in 27 appearances for a goal every 118 minutes – of any English player with at least 10 goals in the Champions League.
Atletico Madrid v Club Brugge
Not many, if any, would have tipped Club Brugge to top Group B ahead of Atletico Madrid, Bayer Leverkusen and Porto, but they have defeated all three to lead with a perfect nine points and zero goals conceded.
One more win for Brugge would see them progress past the group stage for the first time, in their 10th Champions League campaign. By defeating Atletico, they would become the first Belgian side since Anderlecht in 2000 to win four games in a row in the competition.
Brugge are also one goal away from matching their highest goal tally from a single Champions League campaign, with eight goals in 2020-21.
Surprisingly, Atletico have struggled at home in the Champions League, snapping a streak of eight games without a win (D5 L3) by defeating Porto this season.
Brugge's Ferran Jutgla has registered a goal and an assist in each of his past two Champions League games, and if he can manage to do it again, he will join Robert Lewandowski and Leroy Sane as the only players since 2003-04 to have a goal and an assist in three straight games in the competition.
Bayer Leverkusen v Porto
With Brugge seemingly cruising, Porto, Leverkusen and Atletico are likely fighting it out for one automatic qualification spot, and Leverkusen will feel good about their chances as Porto are winless in their last seven away games against German teams (D2 L5).
After defeating Atletico at home on the second matchday, Leverkusen will be looking to win consecutive Champions League home fixtures in the same campaign for the first time since 2014.
Patrick Schick is Leverkusen's focal point going forward, attempting more than twice as many shots (12) as any of his team-mates this Champions League season, but he is yet to score, having missed a penalty against Porto in last week's 2-0 loss.
Porto's Mehdi Taremi assisted both goals in the reverse fixture, marking the first time he has been involved in multiple goals in a Champions League game, while the sending-off of Jeremie Frimpong gave Leverkusen their 11th red card in their history in the competition, trailing only Bayern Munich (21) amongst German sides.
Other fixtures:
Napoli v Ajax
5 – Napoli beat Ajax 6-1 in the reverse fixture at Johan Cruyff Arena, with the five-goal margin marking the heaviest defeat Ajax have ever suffered in European competition.
10 – With one more win, Napoli would become the fourth Italian club to ever mount a 10-game unbeaten streak in the Champions League, with six wins and three draws from their past nine fixtures.
Rangers v Liverpool
5 – Rangers have failed to score in their past five European games against English competition, including a 2-0 loss against Liverpool last week.
35 – Mohamed Salah has scored 35 Champions League goals for Liverpool – only Didier Droga (36 for Chelsea) and Sergio Aguero (36 for Manchester City) have scored more for a single Premier League club in the competition.
Sporting v Marseille
9 – Marseille have lost their past nine away fixtures in the Champions League, and with one more loss they would become the sixth team to ever post 10 consecutive away defeats in the competition, and the first from France.
18 – It has been 18 years since Sporting lost a home fixture against a French side in European competition, with that loss coming against Sochaux in the 2004 UEFA Cup.
Viktoria Plzen v Bayern Munich
31 – Bayern Munich are undefeated in their past 31 Champions League group stage matches (28W 3D) – which is an all-time high – and with one more win they will set the new record for consecutive group stage wins with 11.
32 – Viktoria Plzen have faced 32 shots on target in their first three games of this Champions League campaign – more than any other side. In the reverse fixture, Bayern had 13 shots on target.