Once he graduated from Amherst in 1852, Bliss went on to attend Andover Theological Seminary to prepare for foreign and overseas missions.

By October 1855, he was ordained at Amherst and in November of the same year he was married to Abby Maria Wood.

After being assigned to Syria by the American Board, he and his wife sailed from Boston, Massachusetts, in December 1855.

From October 1858 until 1862, Bliss was in charge of a boarding school in a town just north of Aley called Souk-al-Gharb.

Bliss was named president of the college he had founded and also took on the responsibilities of treasurer and Professor of Bible and Ethics.

He met with the American Board of Commissioners for Foreign Missions where he spoke in support of the resolutions adopted in Beirut.