After Cologne's Germany striker Lukas Podolski netted a 93rd-minute penalty to seal his team's 2-0 win and drop Frankfurt to second-bottom, angry home fans poured onto the pitch at the final whistle.
Frankfurt players had to flee into the changing rooms and were protected by hundreds of riot police, who beat back a group of charging fans and made several arrests.
"The behaviour of the fans is just terrible," admitted Frankfurt chairman Wilhelm Bender.
This is the second Saturday in succession that Frankfurt fans have allowed their emotions to boil over.
A group of 200 fans stoned the team's bus after they were beaten 3-0 at Mainz last weekend and the club cancelled training on police advice early last week before resuming their preparations in secrecy.
Frankurt must now win at champions Borussia Dortmund next Saturday and hope results go their way in their bid to avoid going down after bottom team St Pauli had their relegation confirmed with an 8-1 home defeat by Bayern Munich.