The former flanker had been in charge of Los Pumas for the last six years but has called time on his reign.
Phelan led Argentina to a famous victory over the RBS 6 Nations champions last year but the South Americans failed to win a single match during the recent Rugby Championship.
They arrive in Europe next month, with clashes against England and Italy, either side of a November 16, date with Warren Gatland’s Wales.
“Santiago Phelan will not continue his role as head coach of Los Pumas after six years in office,” said a UAR statement.
“During his career as Pumas coach, Santiago Phelan was in charge of 45 matches in which there were 13 wins, one draw and 31 defeats.
“His debut was on June 7, 2008 against Scotland, while his last game in charge was against Australia in the Rugby Championship in 2013.”
Argentina are set to announce a stand-in replacement for the European tour later today.