The Brazilian midfielder did address supporters directly on the pitch after the final whistle, receiving a framed shirt from the club before delivering a brief but heartfelt message.
"Thank you and take care everyone. Thank you to the players, thank you to the staff. The best thing in this club is you fans."
He later posted a longer tribute on Instagram.
"There are places we pass through in life and there are places that become part of who we are. Manchester will forever be my home. To the city, the club, and every supporter, my sincerest thank you.
"These past four years have been unforgettable, filled with moments my family and I will carry with us for the rest of our lives. There simply aren't enough words to describe the happiness and warmth we've felt here.
"Thank you for every cheer, every memory, and for making us feel at home from the very first day. Forever a Red Devil."
Casemiro joined Manchester United from Real Madrid in 2022 and leaves as a free agent this summer after 161 appearances, 26 goals and two trophies during his four years at the club.
Interim head coach Michael Carrick had praised Casemiro before the match, describing the clarity of knowing his situation as something that allowed the midfielder to give everything right to the end.
"He's been fantastic for us, for me personally, for us as a group. For him to get his head in a place of giving absolutely everything, knowing that it was going to come to an end at the end of the season, knowing the situation — he's obviously had some ups and downs, but to finish so strongly and to see that connection with the supporters is really good to see."