The German club beat Real Betis 2-1 in the first leg of their last-16 tie, 24 hours before the Hammers were due to face Sevilla in the same city.
Uefa had moved the Frankfurt game to a day earlier to avoid the two matches clashing, but footage emerged online of violence breaking out nonetheless.
One clip showed what appeared to be Frankfurt ultras running en masse down a road, armed with sticks, towards West Ham fans in a bar. Missiles were then thrown between the groups.
Another video showed the German club’s followers rushing their English counterparts with sticks and other objects, as scuffles broke out and Hammers fans retreated.
It is not clear what first sparked the altercation but a number of West Ham supporters took to social media to voice their anger at the Frankfurt ultras and the actions of the Spanish police, with claims of rubber bullets being used.