Sejad Salihovic was Hoffenheim's hero and villain in a matter of seconds as he put the hosts ahead, but then received his marching orders in the 10th minute.
Oliver Sorg levelled for Freiburg before Kevin Volland restored Hoffenheim's advantage, which again lasted only a few minutes before Karim Guede brought Freiburg back on terms.
The visitors lost Francis Coquelin to a red card before the interval, yet they took the lead for the first time through Sebastian Freis in the 65th minute.
Tobias Strobl levelled in the 77th minute before the final red card of the game was shown to substitute Admir Mehmedi in stoppage time.
Hoffenheim continued their tradition of scoring early goals this season by taking the lead from the penalty spot in the 10th minute.
Volland was brought down inside the penalty area by Sorg and Salihovic took the responsibility for putting the home team in front from the spot.
He got a little carried away with his celebrations, though, and was provoked into raising his hands towards Julian Schuster. Instead of celebrating his goal, he was sent walking down the tunnel after receiving a straight red card, the fourth of his career.
Sorg then made amends for his foul which conceded the penalty by bringing Freiburg level with his first goal in his 52nd Bundesliga appearance.
His shot from the edge of the penalty area took a deflection of Roberto Firmino to leave Koen Casteels with no chance.
Hoffenheim reorganised their 10 men and regained the lead through Volland in the 25th minute with a fine lobbed finish from a long Jannik Vestergaard ball forwards.
Their lead lasted just a minute longer than their first one, however, with Guede tucking the ball in from close range after Koen Casteels' save was headed back across goal by Schuster.
The first half ended with even more drama, Coquelin picking up two yellow cards in the space of a minute to join Salihovic in the dressing room, where he was subsequently joined by Freiburg coach Christian Streich.
Freiburg took the lead for the first time in the 65th minute when a corner found its way through to Freis at the far post.
Just over 10 minutes passed before the 10 men of Hoffenheim levelled. Strobl picked up possession in midfield after a mistake by Gelson Fernandes and he took a few steps towards goal before unleashing a powerful shot past Oliver Baumann.
Anthony Modeste almost snatched a win for Hoffenheim only to be denied by the post before Mehmedi stole a march on his team mates back into the dressing room, earning a red card for dissent.