The protesters ran through fields and broke through a police cordon to get into the Garzweiler mine.
Police had warned that the mine was not safe and said some officers were hurt as they tried to hold back protesters.
Germany has vowed to go carbon neutral by 2050 but activists say this is not soon enough.
Recent surveys have shown that climate change tops a list of concerns in Germany, with the Green party polling alongside the governing Christian Democrats.
Earlier in the day, protesters temporarily blocked a railway line used to transport coal.
Some of the activists were among between 20,000 and 40,000 protesters who joined a demonstration on Friday in the city of Aachen in support of the school strike movement launched by Swedish teenager Greta Thunberg.