An acronym is a word derived from the first letter (or first few letters) of several other words.  A prime example is SCUBA (self-contained underwater breathing apparatus).  Other examples are NATO (North Atlantic Treaty Organization) and NOLA (New Orleans, LA).

An initialism is an abbreviation that uses the first letter of each major word in a phrase but does not form a new word.  Rather, the actual letters are pronounced.  A couple of examples are EPA for Environmental Protection Agency and FBI for Federal Bureau of Investigation.

Click here for Merriam-Webster’s take on these terms.