While reading the Miami Herald one day in the fall of 1955, songwriter Tommy Durden spotted the headline "Do You Know This Man?" A photograph of a suicide victim accompanied the article. The man had left no identification, but did leave a note that read, "I walk a lonely street." Miami police w ere running the article in the hope that the man's next of kin or friends could identify him. Durden thought that the man's suicide note might provide the basis for a great blues song. He excitedly called his collaborator, Mae Axton, and she agreed. The two of them wrote Heartbreak Hotel in about 15 to 20 minutes at Axton's house. Mae Axton took her demo to Nashville for the annual disc jockey convention at the Andrew Jackson Hotel on November 10, 1955. After hearing the demo in his hotel room, Elvis was ecstatic. He promised Axton that he would record Heartbreak Hotel the next time he was in the recording studio.

Elvis recorded Heartbreak Hotel on January 10, 1956, at RCA's Nashville Studios. It was the second song he recorded for RCA; the first was I Got a Woman. Instrumental backing was provided by Scotty Moore (guitar), Chet Atkins (guitar), Floyd Cramer (piano), Bill Black (bass) and D.J. Fontana drums). Gordon Stoker, Ben Speer and Brock Speer sang the backing vocals. Elvis's first RCA new single, Heartbreak Hotel/I Was the One, was released on January 27, 1956. In April Heartbreak Hotel succeeded Les Baxter's The Poor People of Paris as the nation's number one song. After a seven-week stay at the top, it was replaced by Gogi Grant's The Wayward Wind. Heartbreak Hotel was also number one at the Country Best-Seller chart (for 17 weeks), the Country Juke Box Chart (for 13 weeks), the Country Disc-Jockey Chart (for 12 weeks) and reached #5 on the rhythm and blues chart – the first Presley record to reach the latter chart. Heartbreak Hotel was Elvis's first million-seller and the second record in history to reach all three Billboard charts. (The first was Carl Perkins's Blue Suede Shoes). Total stay on the Top 100 chart was 27 weeks. Elvis sang Heartbreak Hotel on Stage Show (February 11, March 17 and March 24), The Milton Berle Show (April 3) and The Ed Sullivan Show (January 6, 1956). Billboard listed it as the number one single of 1956. Heartbreak Hotel was sung in the 1968 TV Special Elvis, and in the 1970 documentary Elvis - That's The Way It Is.

In 1956 The Cadets recorded a cover version of Heartbreak Hotel for Modern Records (Modern 985). It was the first cover of an Elvis record by black performers. Other recordings of Heartbreak Hotel through the years include those by Star Fredberg (Capitol 3480), a 1956 parody; Roger Miller (Smash 2066) in 1966; Frijid Pink (Parrot 352) in 1970; and Willie Nelson and Leon Russell (Columbia 3-11023), who had a #1 country duet with the song in 1979.