Signed as a 20-year-old for around 18 million pounds ($20.25 million) in 2011, De Gea replaced retired goalkeeper Edwin Van der Sar and made the number one shirt his own over the years.
A four-times winner of the player of the year award at the club, the 31-year-old became the first non-British or Irish player to make 500 appearances for the Premier League club.
"Today marked an unbelievable day for me, I came here from Spain 11 years ago and now I call this my home," De Gea said on Twitter.
"To represent any club 500 times is special but to play for this club, the greatest football club in the world fills me with great emotion. I want to thank everyone that has helped me along the way, my family especially."
In 11 years at United, he has won the Premier League, FA Cup, League Cup and Europa League, keeping 170 clean sheets. He is also the 11th player to play 500 times for United.
Former Wales winger Ryan Giggs holds the record at United with 963 appearances over a career that spanned more than two decades.
De Gea was given an award before Sunday's game to mark his milestone, which was handed over by former manager Alex Ferguson who signed the Spaniard from Atletico Madrid.
"It was the right person to give me the award. He brought me to the club, he trusted me and believed in myself," De Gea said.
"It was great to be there at a full Old Trafford with Sir Alex and it was a great moment."
