The half-time sub had helped change the game for the visitors, arrowing into the bottom corner from 25 yards to launch the comeback. The Hammers then levelled on 80 minutes when Konstantinos Mavropanos headed in at the back post and looked set to push on for a winner.
Please use Chrome browser for a more accessible video player
Kante pulled a goal back for West Ham
Please use Chrome browser for a more accessible video player
Konstantinos Mavropanos headed in West Ham's equaliser
But Kante brought down Kyrell Lisbie with a last-man foul after he had been caught in possession to receive the fourth red card in the past seven meetings between these sides and Lyndon Dykes blasted over a last-gasp chance for the Millwall to clinch it.
Please use Chrome browser for a more accessible video player
Mohamadou Kante took one for the team and saw red for West Ham after he pulled down Millwall's Kyrell Lisbie
It was a dramatic conclusion to a game which lived up to its billing, 14 years on from the last Dockers derby.
The home side overwhelmed West Ham in the first half. Close-range goals from Caleb Taylor and Camiel Neghli from Dykes long throws summed up their physical approach.
Please use Chrome browser for a more accessible video player
Caleb Taylor opened the scoring for Millwall against West Ham
Please use Chrome browser for a more accessible video player
Camiel Neghli extended Millwall's lead
It could have been an even better first 45 for Millwall had Mark Sykes' screamer against the bar from 35 yards gone in.
West Ham had been well short of the intensity levels required for this fixture to that point but changed the narrative after the break. Wave after wave of attack on the Millwall goal eventually brought them the rewards to retain local pride and top spot in the Championship - although a first win at Millwall since 1988 proved elusive.
Allegation of spitting
On 65 minutes, the match was stopped when Millwall goalkeeper Filip Marschall made an accusation that West Ham forward Taty Castellanos had spat at him. Play resumed without any action taken.
Afterwards, Millwall boss Alex Neil said: "I haven't asked [Marschall] about it. I'm sure there will be footage of it or not of it if it didn't happen. I'd be extremely surprised if Filip has made an accusation and nothing has happened. The fourth official said there was an accusation of spitting."
West Ham boss Nuno Espirito Santo said: "I'm aware of the allegation. I didn't see the image, I didn't speak with Taty. I cannot go much further on that. I'm going to look at the images but I cannot answer."
Key moments at the Den
16: GOAL! Caleb Taylor forces the opener in after Mads Hemansen saves from Mark Sykes and Tairyk Arconte when Lyndon Dykes' long throw caused chaos in the West Ham box.
45: OFF THE BAR! Sykes cracks the ball against the crossbar from 35 yards out.
Please use Chrome browser for a more accessible video player
Mark Sykes hit the crossbar during the first half
45+1: GOAL! Camiel Neghli scores Millwall's second from close range after another Dykes long throw comes to him in the box, capping a brilliant first half for the Lions.
46: SUBS! West Ham make a double change at the break with Mohamadou Kante and Pablo sent on.
52: CHANCE! Jarrod Bowen's shot is parried by Filip Marschall and the goalkeeper just reacts in time to prevent Kante tucking in the loose ball.
Please use Chrome browser for a more accessible video player
Millwall 'keeper Filip Marschall produced a brilliant stop to deny West Ham
67: SAVE! A stunning one-hand stop from Marschall keeps out Pablo's header.
74: GOAL! Kante arrows a low shot into the bottom corner from 25 yards to pull one back for the Hammers.
76: SIDE-NETTING! Jarrod Bowen is teed up in the box by Taty Castellanos but his shot is deflected just the wrong side of the near post as the Hammers mount wave after wave of attacks.
80: GOAL! Konstantinos Mavropanos heads in Manor Solomon's cross from a short corner at the back post to level it up!
89: RED CARD! Kante is sent off after bringing down Kyrell Lisbie when he was clean through on goal.
90+3: OVER! Dykes sends a half-volley flying over the bar from inside the West Ham box.
The managers
Millwall's Alex Neil:
"Mixed emotions. It was an unbelievable effort from the players. they left everything on the pitch, as you would hope for. We just ran out of steam as the game wore on. There was a lack of freshness in options, particularly at the top end of the pitch. I thought [Lyndon Dykes] and [Tairyk Arconte] were excellent, caused them all sorts of problems in the first half. But once we hit about 60-65 minutes, we really tired.
"So 2-0 up, brilliant first half, probably should have been more. They then changed their shape to a 3-5-2 and we found it really difficult to get out. We lost energy in the middle, we lost energy in the top line and ended up sinking and sinking.
"The frustrating thing from my perspective is the goals come from a 30-yard shot from outside the box and a second-phase set-play. All in all, I couldn't ask any more of the lads."
West Ham's Nuno Espirito Santo:
"Clearly the first half we didn't go well in the game, we didn't start well, we were not precise, we lost balls, we didn't deal with the physicality of Millwall. They are so good and strong, they took advantage of the throw-in, the way we can see things happening.
"Disappointing on that part, we knew what we were going to find but we didn't do well.
"But much improved in the second half and the way the game went, it's a positive. Not what we wanted but the way the boys reacted to a bad first half was good and positive."
On Kante's red card: "He came into the game very well, a beautiful goal but then a big mistake and then it was the right decision to take it and avoid something tragical.
"He's a very young player, a lot of things to improve - we have many in our squad - so I hope this is a lesson for his future."
What the result means and next fixtures...
