About 200 people from Wales helped the elected Republican government fight the fascist forces of General Franco.
Carwyn Jones said he was "honoured" to lay a wreath at the brigade's commemorative stone in Cardiff.
He said it was "a tribute to the many brave men and women who risked all in the fight against fascism".
The Welsh contingent - a third of whom were miners - joined an estimated 45,000 international volunteers from 54 countries who sought to defend the Spanish government against Franco's rebel forces in 1936.
More than 500,000 people died - 33 of them from Wales - during the three-year conflict, about 200,000 of them in combat.
Following his eventual victory in 1939, Franco ruled Spain as a dictator until his death in 1975.
"We must never forget the courage and sacrifice of the International Brigade," Mr Jones said in advance of the memorial event at Cathays Park on Saturday.
"Their determination and valour in support of democracy and liberty is a legacy that will endure."
The commemoration event for the Welsh volunteers has been organised by the GMB union.
Regional political officer Mike Payne said the event showed Wales "is and always has been a tolerant place to live and work".
He claimed since the vote for Brexit the "political discourse" in the UK had "not been in keeping with our firmly-held principles of liberty and democracy".
"Wales has always been outward facing and has always taken its international responsibilities seriously," Mr Payne said.
"The sacrifices and the courage of those men and women who left Wales to fight against a fascist dictator in Spain are an example of this."
The first minister has paid tribute to the Welsh volunteers who fought for the International Brigade in the Spanish Civil War which began 80 years ago.