He has served as a Palestinian delegate to the Netherlands (1987–1990), to the United Kingdom (1990–2005), the Holy See, Vatican (1995–2005), and in Washington, D.C. as the head of the PLO mission (2005–2008).

[1] Safieh is an experienced diplomat, having served in the three most politically significant capitals: London, Washington, and Moscow.

[3] In May 2008, Afif Safieh was appointed to serve as the Palestinian ambassador to the Russian Federation, he presented his letter of credentials to President Medvedev on September 18, 2008.

It was reported in March 2009 that he had been dismissed from this post by Palestinian president Mahmoud Abbas, apparently because he had spoken at a rally organised by Hamas to protest against Israeli actions during the 2008–2009 Israel–Gaza conflict.

[5][6] In September 2014 he was awarded by the Bethlehem University the degree of Doctor of Humanities, Honoris Causa.