The attacking pair helped the Lions of Teranga to a 3-1 win against Burundi in Dakar.
Senegal are very much favourites to top the group, which also includes Niger and Namibia, and it was two of their Premier League stars who ensured they would be leaving the match with all three points, after a close start between the two sides.
Diouf, who scored 12 goals for Stoke in his first season since arriving from Hannover, put Senegal ahead in the 62nd minute, lashing home a volley in the middle of the Burundi area.
Mane, who himself scored 10 times since arriving in the Premier League this summer, including the fastest ever hat trick, wrapped up the win in injury time, as Burundi piled forward leaving space at the back for the Southampton forward to utilise his devastating pace. The 23-year-old ran from deep to get on the end of a ball by midfielder Stephane Badji, finishing low in the far corner superbly.