The pair beat Twilight colleagues Robert Pattinson and Kristen Stewart to top the list, taking home box office earnings of $4.2 billion (£2.7 billion) to the real-life lovers' $2.5 billion (£1.6 billion).
Original Transformers duo Shia LaBeouf and Megan Fox came third in the ranking compiled by Forbes and Box Office Mojo with a total of $1.5 billion (£972 million), while Iron Man's Robert Downey Jr and Gwyneth Paltrow finished just behind on $1.2 billion (£777 million).
LaBeouf appears again at five with Fox's Transformers successor Rosie Huntington-Whiteley. The pair pulled in $1.1 billion (£712 million) from their only team-up to date in 2011 sequel Dark of the Moon.
Leonardo DiCaprio and Marion Cotillard are the only couple to land in the top ten for starring in a non-franchise film, finishing ninth with $825 million (£534 million) for Christopher Nolan's Inception.
Watson, Grint and their Harry Potter co-star Daniel Radcliffe were revealed to be worth close to £100 million ($154 million) collectively in Heat's Under 30 Rich List published in November.
> Harry Potter video: Watch Rupert Grint and Emma Watson film kiss
The full top ten is as follows:
1. Rupert Grint and Emma Watson, Harry Potter - $4.2b
2. Robert Pattinson and Kristen Stewart, Twilight - $2.5b
3. Shia LaBeouf and Megan Fox, Transformers 1, 2 - $1.5b
4. Robert Downey Jr and Gwyneth Paltrow, Iron Man - $1.2b
5. Shia LaBeouf and Rosie Huntington-Whiteley, Transformers 3 - $1.1b
6. Johnny Depp and Penelope Cruz, Pirates of the Caribbean 4 - $1b (£648m)
7. Orlando Bloom and Keira Knightley, Pirates of the Caribbean 1-3 - $963m (£606m)
8. Tobey Maguire and Kirsten Dunst, Spider-Man - $890m (£576m)
9. Leonardo DiCaprio and Marion Cotillard, Inception - $825m
10. Chris Noth and Sarah Jessica Parker, Sex and the City - $703m (£455m)