South African veteran du Plessis hit an unbeaten 95 as three-time champions Chennai Super Kings (CSK) beat Kolkata Knight Riders (KKR) by 18 runs to go top of the standings with Royal Challengers Bangalore and Delhi Capitals.
Bangladesh's star all-rounder Shakib Al Hasan was replaced by West Indies' Sunil Narine in Kolkata's line-up for this match.
Du Plessis shared an opening stand of 115 with Ruturaj Gaikwad who hit four sixes and six fours in his 64 at the start of what Kolkata captain Eoin Morgan called "a hell of a game of cricket".
He watched patiently as Moeen Ali smashed 25 off 12 balls and M.S. Dhoni made 17 runs off eight.
Du Plessis then took over, coming agonisingly close to a first IPL century before the overs ran out.
"It is the most fluent I have felt so far," he said of the innings that included four sixes and nine fours.
Chennai's 220 for three looked formidable, especially as Kolkata lost opener Shubman Gill first ball and slumped to 31 for five with seamer Deepak Chahar claiming four victims.
But Andre Russell hit 54 in 22 balls, including six sixes, and Dinesh Karthik made 40 off 24 and Kolkata were back in the game. Pat Cummins laid on an explosive tail end finale.
The Australian fast bowler passed 50 in 23 balls smashing all the Chennai bowlers around the ground.
England's Sam Curran conceded 30 in one demoralising over.
Kolkata needed 20 off the final over with Cummins on 66 off 34 balls with six sixes and four fours.
Their hopes were ended when Prasidh Krishna was run out on the first ball.
"It was a proper batsman's game," said Du Plessis who was named man of the match.