Cullen has been part of Hamilton's small inner circle since 2016, assisting the British driver as recently as the season opener in Bahrain a fortnight ago.
However, ahead of the second round in Saudi Arabia this weekend, Hamilton revealed he has split with the 48-year-old New Zealander.
"For the last seven years Angela Cullen has been by my side, pushing me to be the best version of myself," said Hamilton, 38. "I am a stronger athlete and a better person because of her.
"So today I hope you'll join me in wishing her the very best as she takes her next steps to pursue her dreams. Thank you for everything Ang, I can't wait to see what the future has in store for you."
Cullen added: "Exactly seven years ago on this day I was standing in the F1 paddock for the first time at the Australian GP. Today I'm excited to share I'm off on my next adventure.
"I am so grateful and blessed to have had this incredible journey in F1 and I know my story will continue.
"Thanks to the MB [Mercedes-Benz] team, who have been my family for the past seven years.
"And Lewis Hamilton you GOAT!! It's been such an honour and pleasure to stand along side you I'm so proud of you and everything you have achieved.
"Thank you for supporting me, believing in me and showing me the limitless potential we all have within us.
"I am so excited to watch the next chapter for you. There's nothing you can't do.
"Don't stop believing. Life's journey is one big wave. Keep riding. Dream big. As dreams do come true. Forever by your side. Still we rise."