Pokemon main man Ash Ketchum and his loyal Pikachu are set to leave the anime show after 25 years.
On Friday, producers said a new-look series will begin in April 2023, reports BBC.
Actress Sarah Natochenny, who has provided the English voice for Ketchum and various other characters since 2006, said it had been "an extraordinary privilege".
"No matter what lies beyond his final chapter, he'll live forever in the hearts of many generations to come."
The Japanese anime show, which has also spawned several movies, has followed Ash in his quest to become a Pokemon master trainer since 1997 when the character met the electric mouse creature Pikachu on his 10th birthday.
And last month, he finally completed his quest when he won the Pokemon World Championship.
The show will introduce two fresh protagonists from next spring - a young girl named Liko and a boy named Roy, who will be accompanied by three Paldea starter Pokemon.
"It will represent everything [fans] love about Pokemon animation, including action, adventure, friendship and Pokemon," the producers said.
Before that, on 13 January, an 11-episode epilogue series to the current run, titled Pokémon Journeys in the West, will tell the final chapter of Ash and Pikachu's story.
Responding to Natochenny, who took over vocal duties from Veronica Taylor at the end of series eight, fans have been paying their tributes online.
"I've been a fan of this anime since it came to the US when I was in fifth grade," posted one.
"As a lifelong fan, I am truly grateful for your dedication to a character that defines many of our childhoods. Thank you for being such an excellent role model."
Realised his dream
"Thanks for all the adventures you and Veronica Taylor have given us through seven regions," wrote another.
"For the countless Pokemon you've voiced alongside Ash, and for giving a voice to a character that is as iconic as Goku is to DBZ. Ash has realised his dream of becoming a Pokémon master and champ."
The Pokemon franchise has grown to include Pokemon Go, a landmark mobile game using online maps and augmented reality to place the characters in real-world locations.
The latest Pokemon video games for the Nintendo Switch have already sold more than 10 million copies since their release at the end of last month.
