The comedy writer said that he expects the Fox animation to last at least "four or five" more years, and will end the show if people grow tired of it.
"It's not coming to an end, not yet," he told BBC Breakfast. "There are more [seasons] to come. Right now there's no end in sight.
"It's got another four or five years of life left. When people start getting sick of it we'll shut it down."
MacFarlane added that British Family Guy fans often "get" the show's humour better than Americans.
"You guys get a lot more of the jokes than in the States. A lot of it goes over the heads [of Americans]."
The actor also spoke about his upcoming appearance at this year's BBC Proms, where he will appear in a show paying homage to Broadway musicals past and present.
On his singing career, he said: "I trained [as a singer] when I was a kid. When Family Guy got going, it became clear that it was a useful skill to have with the musical numbers.
"In order to sell those numbers it's got to sound good, so I started training again."
Seth MacFarlane will appear at the Royal Albert Hall on Monday, August 27. His performance will be broadcast live on BBC Radio 3 from 8pm.
Watch Seth MacFarlane perform 'Singin' in the Rain' below: