The veteran pop star, who first charted with Holiday back in 1984, has sold a total of 17.8 million singles in the last 28 years.
But while Rihanna is a fair way behind her in second spot with a total of 11.4m singles sold, she has managed to do that in just seven years.
And RiRi has sold three million singles in the last year alone - leading to speculation that she could be in the No 1 spot herself before too long.
Kylie Minogue was in third spot with 10.2m singles and Whitney Houston was fourth with 8.5m. Lady GaGa rounded out the top five with 7.3m.
The data was provided by The Official Charts Company, and here is the top 10 in full...
1. Madonna (17.8m)
2. Rihanna (11.4m)
3. Kylie Minogue (10.2m)
4. Whitney Houston (8.5m)
5. Lady GaGa (7.329m)
6. Britney Spears (7.324m)
7. Beyoncé (6.9m)
8. Celine Dion (6.7m)
9. Mariah Carey (6.62m)
10. Olivia Newton John (6.61m)