Then England manager Sven-Goran Eriksson caused a major surprise by naming untested teenager Theo Walcott in his squad for Germany, with Defoe one of the players who missed out.
But the in-form Tottenham striker has staked his claim for a first-team spot with five goals in his last three internationals as England look to book their place in South Africa with a positive result against Croatia at Wembley on Wednesday.
And Defoe remembers how Beckham responded after being sent off in the 1998 finals against Argentina in France and now has more than 100 caps to his name. Defoe said: "It was disappointing to miss out on 2006 but when you go through disappointments in life, it's about how you react and come back from them.
"If you look at the most talented players, they all have to do that. If you look at David Beckham, he got sent off in the World Cup in 1998 and had to bounce back, which he did by getting a goal against Greece a few years later to get us to another finals.
"To do what he has done since, to get all those caps and have an incredible career, is unbelievable. You look at players like that and learn from them. You've just got to keep your head up and keep working and hopefully you will get another chance - and that's what I want with this next World Cup."
Defoe wants to start against Croatia but is adamant England clinching their spot at South Africa 2010 takes priority over his own personal ambitions. He said: "Of course, I'd like to be in from the start on Wednesday. You want to play every game for your club and for your country.
"Everyone wants to play. You don't want to sit on the bench. It is a massive game against Croatia. We all remember what happened last time against them at Wembley and we don't want to have that feeling again. It is hard to put in words what it felt like two years ago. It was like 'it's all over' and we were out of the European Championships before making the finals.
"We want to forget about that and put things right. We have moved on since then and there has been a great improvement. Everyone wants to play but I don't want to say too much. Three points on Wednesday is the most important thing."