Dhoni, who promoted himself to number four, hit two fours and as many sixes in his knock after coming at the halfway stage of the innings after his side was sent into bat at the Newlands in the Group B match.
Chennai lost wickets at regular intervals and looked like they would settle below 150 but the 50-run stand from 4.2 overs between Dhoni and S Badrinath (27 not out) for the sixth wicket saw them go past that mark.
The last two overs yielded 27 runs, with the penultimate bowled by Dirk Nannes, producing 19 and that saw Chennai reach a challenging total.
Badrinath was the second highest scorer while all the other batsmen, except for Albie Morkel (4), contributed in the 20s.
For the Lions, Aaron Phangiso grabbed two wickets for 17 runs from his quota of four overs while Sohail Tanveer, Nannes, Chris Morris and Zander de Bruyn took a wicket each.
The Chennai openers Faf du Plessis (25) and Murali Vijay (22) began on a confident note with the former launching Nannes for a huge six in the second over and then gave the treatment to Tanveer with three fours from the next over.
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Vijay, who played second fiddle so far, then struck an effortless six off Nannes to take Chennai score to 43 for no loss at the end of fifth over.
The breakthrough for the Lions was provided by Morris with Phangiso taking a stunning catch to get rid of du Plessis who consumed 20 balls for his 25.
Phangiso, who had dismissed Sachin Tendulkar in Lions' previous match, ran back from the point region, dived full-length and pouched the ball before thudding himself into the ground.