In order to achieve combo, you need to destroy the set of marbles and after that, before your next shot, another set (or more of them) should be automatically destroyed when marbles collide to close the gap.
 
Creating combos can provide you with special marbles which might be very helpful:

Colorful – Create two combos with marbles on the ends in green or yellow color. Colorful ball can replace one marble of whichever color in its surroundings.

Bomb - Create two combos with marbles on the ends in purple or red color. The bomb destroys several balls in its surroundings.

Color bomb – Create two combos with marbles on the ends in blue or orange color. Color bomb destroys all the marbles of the same color.

Color mist – Create a triple combo ending with red or yellow marble. This marble creates a cloud changing all the marbles in its reach to same color.

Color replacer - Create a triple combo ending with blue or purple marble. It turns all marbles of the color you hit into the color of the Replacer.

Fireball - Create a triple combo ending with green or orange marble. It destroys all the marbles in its path.