The Bachata King retains his crown on the music publication's annual list, which ranks artists based on chart performance, touring revenue, and social media activity, reported Billboard magazine.
Santos, 34, has his 2014 album Formula, Vol 2, to thank for his top spot as the project continued to sell well in 2015, becoming the year's second biggest seller.
In addition, his single, "Propuesta incedente", became the longest running hit on the Hot Latin Songs Top 10 chart in history, and four of his hits were among the 10 most-streamed songs of the year.
Rounding out the top five are Enrique Iglesias, Colombian star J Balvin and singer-songwriter Nicky Jam.
One notable act on the Top Latin Artist list is regional Mexican act Ariel Camacho y Los Plebes del Rancho at 10.
Camacho died in a car crash following a concert in Mexico in February (15).