The Lions were leading at half-time through goals from Caleb Taylor and Camiel Neghli but the Hammers hit back through Mohamadou Kante and Konstantinos Mavropanos.
West Ham, who made the short trip across the River Thames sitting top of the Championship and looking for a fifth straight win, finished their first meeting with their fierce rivals since 2012 with 10 men after Kante was sent off.
London's Metropolitan Police had 400 officers on hand in a bid to ensure there was no repeat of the violence which has marred this fixture in previous seasons.
There were no immediate reports of any trouble among spectators.
Millwall went ahead in the 16th minute after Lyndon Dykes caused chaos with a long throw into the box.
With Hammers centre-half Mavropanos off the pitch while receiving treatment, no one from the away side dealt with the ball until it fell at the feet of Mark Sykes, whose point-blank shot produced a superb save from Mads Hermansen.
But Tairyk Arconte got to the loose ball first and played it back across goal for Taylor to fire home at the far post.
Millwall kept pressing forward and another long Dykes throw led to a second goal before the break, with Neghli tucking the ball away.
Hammers manager Nuno Espirito Santo threw on Kante and Pablo Felipe at the break to add a bit of strength to his flimsy side.
It was Kante who started the West Ham revival in the 74th minute with a low drive into the corner.
West Ham equalised with 10 minutes left when Mavropanos headed home Manor Solomon's cross.
The Hammers looked as if they might go on to score a winning goal until last man Kante was shown a red card for pulling back fellow sub Kyrell Lisbie as he raced through on goal.