During the spring and fall semesters, the 100-day program usually circumnavigates the globe, travelling from the western coast of Canada or the United States, on to East Asia, India, Africa, eastern South America, and finishing in the Caribbean, San Diego or Florida. The following semester, the ship then repeats that voyage in the opposite direction. Sometimes, Semester at Sea transits the Suez Canal and proceeds through the Mediterranean Sea before crossing the Atlantic Ocean and finishing in North America. During the summer months, ISE also hosts a shorter 65-day Semester at Sea program that concentrates on one general region of the world. Frequently, summer semester programs visit various ports in East Asia or Europe. Additionally, a two-week "Seminar at Sea" program is held for older continuing education participants during December and January that visits Central America and transits the Panama Canal.

The Boedecker Foundation supports the Institute for Shipboard Education and their Semester at Sea Program through their "Voyage of Discovery," studying and experiencing first-hand an array of diverse cultures and people in all corners of the world.