Two goals in nearly as many minutes from the Senegalese international in the first-half sealed the victory, with Spurs failing to comeback despite some brighter play in the second-half.
Jürgen Klopp resisted the urge to restore Loris Karius to his starting 11 after a poor couple of performances from Simon Mignolet, whilst Lucas Leiva continued alongside Joel Matip in defence due to the absence of Dejan Lovren.
Mauricio Pochettino opted to continue with a four-man defence, leaving Kevin Wimmer out.
The game started at a quick pace as Christian Eriksen blasted an effort over at one end, with Toby Alderweireld's block denying Roberto Firmino at the other end.
Mane hands Reds the advantage and quickly doubles it
It took just 15 minutes for the first goal to come, Mane netting on just his second start since returning from the African Cup of Nations. Ben Davies didn't cover himself in glory in tracking the winger, who ran onto a beautiful through ball from Georginio Wijnaldum to slot past Hugo Lloris.
The second came just two minutes and 15 seconds later, Mane again the scorer. Latching onto another mistake, this time by Eric Dier, he set up Adam Lallana to shoot and after the Brazilian's was effort saved by Lloris, it fell into Mane's path to rifle in.
Mane's goals failed to inspire a Spurs response, with Lloris' save preventing the winger from getting a hat-trick soon after, before Mignolet was finally forced into action, saving nicely from Heung-Min Son after the winger found himself with room inside the area.
Davies, in the Tottenham team for the injured Danny Rose, really found himself struggling against Mane, leaving Dier forced to come across and cover with a fantastic tackle after Coutinho's pass set Mane free past the Welshman.
Spurs unable to respond in second-half
Tottenham did begin to inflict a little more pressure in the Liverpool penalty area as the game entered the second half, and did manage to put the ball in the net.
Eriksen's free-kick was met by an offside Kane who struck the ball against the post, before the rebound was put in following a blow of the referee's whistle.
Liverpool were looking to continue their impressive record against sides around them, and a second half plan to slow the game down seemed to be working as a cluster of yellow cards were handed out by referee Anthony Taylor, totalling eight by the end of the evening.
Before being replaced by Emre Can, Coutinho nearly made it 3-0, striking through the legs of Alderweireld, the ball finishing up narrowly wide of the left post.
That miss didn't matter though as Tottenham, who ended the game slinging long balls in towards Kane, had ran out of fresh ideas.
Liverpool move back into the top four, at least until Manchester City play on Sunday, with victory closing the gap on second-placed Tottenham to a single point.