The 25-year-old moves to Tyneside for an undisclosed fee, rumoured to be in the region of £11m.
The Dutch international, who can operate as an attacking midfielder and a striker, scored 78 goals in nearly 250 appearances for Ajax after breaking through their famous youth system in 2007.
De Jong's brother Luuk spent six months on loan at St James' Park last season, but failed to find the net.
Siem de Jong told the club's official website: "It is great to have signed for Newcastle. It is a big club which my brother told me all about, so I already feel good here.
"I had been at Ajax a long time and wanted a new challenge in a new environment and a new country. Coming to Newcastle is a great opportunity and the chance to play for a club like this in the Premier League was one I could not turn down.
"I am looking forward to starting training and meeting my new teammates and hopefully we can have a successful season."