This seems like a ridiculous question considering all English versions of the Bible include the phrase “in Ephesus” in the first verse (except the RSV, which almost always favors unorthodox translations). But reading the footnote of a worthwhile translation (ESV or NASB) reveals, “Some manuscripts do not contain ‘in Ephesus.’”
As far as we know, only three manuscripts do not contain the phrase, however, they are three significant copies of the original NT writings. More doubts arise in light of the fact that some of the earliest commentators show no awareness that the letter was addressed to Ephesus; one thought it was written to Laodicea.
Given that Paul spent the majority of his known ministry in Ephesus, traveling there on multiple occasions, significantly impacting the city’s economy to the point of a riot, and bidding a sorrowful farewell to the Ephesian community (Acts 19:21-41, 20:36-38), we would expect a considerable amount of personal appeals, greetings, etc. as was his custom in other letters. However, this letter is by far Paul’s most impersonal and general, including phrases such as, “I have heard of your faith in the Lord Jesus and your love toward all the saints” (1:16). No Ephesian individuals, groups, or issues are addressed in the entire letter.
With the considerable evidence against Ephesian reception, at least two things prevent complete dismissal. First of all, the letter had an intended recipient. Even among those copies that do not include “in Ephesus,” the text literally reads, “To the saints who are and who are faithful in Christ Jesus.” Without a designation the remaining wording is clumsy. Secondly, copies of this letter were designated to the Ephesians from early in its history. Ancient copiers would not arbitrarily add words to sacred texts. The only sufficient reason for including the phrase, “in Ephesus” is that it was copied from what was believed to be an authentic copy.
Perhaps the best way to decipher the destination comes from the similarity between this letter and Colossians. Explanations in both point out that they were delivered by Tychicus and that Paul expected them to be circulated throughout Asia Minor. Ephesus would be a reasonable starting point as it was the gateway city to the region. It had influence because of geography, population and because of the temple shrine to Diana (or Artemis), containing an image said to have fallen from heaven to earth, making it the religious center. When Jesus addresses the churches throughout Asia Minor in Rev. 2, he starts with Ephesus.
Because he spent a considerable amount of time in Ephesus, Paul wouldn’t have to address specific issues by letter and would certainly have “heard” of the faith and love of those in the region. Instead, he could write a general theological letter reminding Christians of their position before God so that they can live it out, regardless of their circumstance or situation. Whether or not we can claim with absolute certainty that this book originally included the phrase “in Ephesus,” we still have an invaluable resource for anyone to live out his or her faith in Jesus.
