Italy was eliminated after a scoreless draw against Sweden on Monday produced a 1-0 aggregate loss.
The Italians have only failed to qualify for the tournament once before - missing out on the 1958 finals in Sweden - after not entering the first World Cup in 1930.
Here we take a look at some of the biggest shocks from qualifying campaigns gone by.
Gian Piero Ventura has confirmed that he intends to resign from his post as Italy coach after they failed to qualify for the World Cup for the first time in 60 years. Needing to beat Northern Ireland in their final game of the three-team group, the Azzurri slumped to a 2-1 loss in Belfast. Resignation? I have to evaluate an infinity of issues. Play-offs are decided by episodes and they went against us but you can understand that when you're at fault.
"We have this tendency to warm up three at a time, then after five minutes we change and another three go", the 36-year-old said. "I have not yet spoken to the president", said Ventura.
OR man claims he was sexually assaulted by George Takei
Stern's co-host Robin Quivers asks. "People say outrageous things on Howard Stern ". "[But] you never sexually harassed anyone". Brunton then said he pushed the actor off of him and went to sit in his auto until he was sober enough to drive himself home.
At 39, the 175-times capped Buffon had announced that the finals in Russian Federation would be his last as a player for the national side.
Another Rome resident Enrico Doddi summed up the national disappointment, saying: "You can not have a good World Cup without Italy".
Sweden survived wave after wave of Italian attacks in the second leg of their European playoff on a night of unremitting tension and drama at a disbelieving San Siro.
"This is incredible! This player has just stopped to play with Sweden one year and a half ago and we are still here talking about him", Andersson said.
Buffon made 175 appearances for Italy and was also a runner-up in the 2012 Euros. "At the time I just thought perhaps it was better that Insigne come on instead".
"Apocalypse Azzurra", said the headline of La Stampa newspaper, referring to the unofficial name of the team whose bright blue jerseys reflect the azure of the Mediterranean Sea.