Maccabi Tel Aviv's progress remained on hold after an 89-87 defeat at Montepaschi Siena, while Barcelona, who booked their top 16 berth last week, made it seven wins out of seven as their guard Juan Carlos Navarro marked the 15th anniversary of his debut in grand style.
Zalgiris, who won Europe's premier club basketball competition in 1999 but started this campaign as one of the dark horses, blew away the highly fancied Spanish side Caja Laboral Vitoria 82-45, which left the 2005 runners-up facing early elimination.
Croatian shooting guard Marko Popovic led the Lithuanian side with 19 points while former Chicago Bulls forward Andres Nocioni cut a forlorn figure at the other end with 10, as Caja Laboral slumped to their sixth defeat in seven games.
Quadruple joy for perfect Spaniards
"No one believed we could top this group at this stage and it's not enough because this is only a build-up for the top 16," Zalgiris coach Joan Plaza told the competition's official website.
"I am proud to be coaching this group of players and we want our fans to push us further every week. The team's character is epitomised by Rimantas Kaukenas, who had surgery last Friday and played his heart out today," added the 48-year old Spaniard.
Caja Laboral coach Zan Tabak said his team were a pale shadow of the side that won the 2010 Spanish league title after they reached four successive Euroleague Final Four tournaments from 2005-08.
"My team has two big problems, mental and physical," the former Croatia centre said.
"Physical problems we can solve quickly but mentally we really need to do a big job because we have lost our confidence and our self-esteem is very low."
Six-time winners and last season's runners-up CSKA Moscow cruised to a 78-61 win over Partizan Belgrade while Unicaja booked their ticket with a 63-48 home win against Polish title holders Asseco Prokom Gdynia.
Besiktas Istanbul also progressed with an 83-72 home defeat of Germany's Brose Baskets Bamberg after American guards Patrick Christopher and Curtis Jerrells combined for 37 points.
The 32-year old Navarro, who guided Barcelona to both their Euroleague titles and Spain to the 2006 world title as well as two successive European Championship gold medals, produced a game high 24 points in Barcelona's 90-66 home win over Lietuvos Rytas on Thursday.
Video clips of highlights from Navarro's career were shown on a giant screen before the match in the Palau Blaugrana and 15 jerseys with his name were handed out to fans to commemorate the milestone before the versatile shooting guard showed he was still able to hold back the years with a vintage performance.
"I started to play in this building when I was 15 years old and this game brought a lot of memories," said Navarro.
"I am proud of how I am treated in Barcelona and I still have some playing years ahead of me. The key is to take care of your body and work hard. I was nervous in the build-up to this game but in a different way than in 1997," he added.
Siena and Maccabi produced the most dramatic match of the round as the Italian side celebrated their fourth successive win after beginning with three defeats and stayed on course to advance from a tough preliminary pool.
The lead kept changing hands in a see-saw battle before centre Tomas Ress scored five unanswered points for the home side to put the game beyond Maccabi's reach in the final minute.
Playmaker Bobby Brown led Siena with 16 points while American centre Shawn James kept the visitors afloat with an outstanding solo effort at the other end, hitting all his nine shots from the floor as he registered 22 points and 12 rebounds.
Holders Olympiakos Piraeus also notched a fourth consecutive victory and moved closer to the top 16 with a 75-53 home rout of Anadolu Efes Istanbul, while eight-time winners Real Madrid produced a strong second half to beat Khimki Moscow 104-81.
Maccabi, Zalgiris lose unbeaten records
Olympiakos hand Nocioni sour Euroleague return