Kieron Pollard smashed Sandeep Sharma for a six over long-off in the first ball of the final over as MI surged past Kings XI score of 168 for 5 by scoring 170 for five.
Pollard remained unconquered on 28 off 12 balls and put on 44 runs in only 15 balls for the unfinished sixth wicket with Aditya Tare (16 off 6 balls) at the Wankhede Stadium.
Prior to their quick-fire partnership, MI were put on the victory path by significant contributions from opener C Gautam (33), skipper Rohit Sharma (39) and Corey Anderson (35).
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The dismissal of Sharma and Anderson in successive overs brought Punjab back into the game but Pollard and Tare shattered their hopes.
It was MIs first win in six games. It was also their their first game at home in this edition and they have now extended their winning run at this venue to nine since the last edition.
It was Punjab's first defeat after a glorious winning streak of five out of five.
Mumbais run-chase started on a none-too-promising note when they lost opener Ben Dunk in the fifth ball of the innings and also Ambati Rayudu to be down 33 for two.
Dunk was caught brilliantly by a diving Wriddhiman Saha behind the wicket off by Sandeep Sharma who also accounted for Rayudu by trapping the batsman in front with a ball that moved in sharply and also kept low.
Chidambaram Gautam, promoted in the order in yet another new opening combination for the title holders, and Rohit Sharma then repaired the innings with a stand of 47.
After the power play, MI were 49 for two and then advanced to 70 for 3 following the exit of Gautam who was dismissed by Rishi Dhawan.
New batsman Anderson smashed a six off Dhawan over long on to make a good start. The left hander from New Zealand, whose highest score has been 39 batting at no. 3 against Chennai Super Kings, then hit left-arm spinner Akshar Patel for three fours and a six in the next the 13th to swing the game in MIs favour. Patel conceded 20 runs in that his last over for expensive figures of 0 for 40.
Teams: Mumbai Indians: Ben Dunk, Rohit Sharma (c), Corey Anderson, Ambati Rayudu, Kieron Pollard, Aditya Tare, Harbhajan Singh, CM Gautam, Jasprit Bumrah, Zaheer Khan, Lasith Malinga.
Kings XI Punjab: Cheteshwar Pujara, Virender Sehwag, Wriddhiman Saha, Glenn Maxwell, David Miller, George Bailey (c), Rishi Dhawan, Mitchell Johnson, Akshar Patel, Laxmipathy Balaji, Sandeep Sharma.
Mumbai vs Punjab preview: Embarrassment for MI despite riches
Title-holders Mumbai Indians would be keen to end their dismal five-match losing streak but the task is easier said than done as they will clash against table toppers Kings XI Punjab in an Indian Premier League match at the Wankhede Stadium here on Saturday. The stadium was a mini fortress which could not be breached in eight attempts last year as MI went all the way to clinch the title for the first time.With the IPL action shifting to India after the initial phase was held in the UAE, MI would be eager to turn around their floundering fortunes after suffering five straight defeats in Dubai, Abu Dhabi and Sharjah.
Kings XI Punjab, on the other hand, would be equally earnest to ensure that their five-match winning streak in the UAE is not snapped by last year's champions.
Punjab have batted, bowled and fielded extremely well in the first phase of the T20 League and another victory at the cost of the struggling MI would enhance their last four qualifying hopes which are already bright.
It has been Mumbai's batting, more than their bowling, which has caused their slump thus far in the tournament. MI have tried out a few opening combinations and failed miserably with captain Rohit Sharma, his Mumbai Ranji Trophy teammate Aditya Tare, former Australia cricketer Mike Hussey and new signing Ben Dunk, also an Aussie, all failing to get going.
The middle order too has performed dismally barring the last game against Sun Risers Hyderabad at Dubai when Kieron Pollard at last found form with a blistering knock of 78 off only 48 balls with six sixes and three fours.
But the powerfully built West Indian all-rounder's stupendous effort went in vain as MI slumped to a 15-run defeat chasing SRH's challenging score of 172.
For MI to get their floundering campaign on track, all the top order batsmen need to find form quickly. While MI batting has been a big let-down, the bowlers have fared only slightly better with Sri Lanka's World T20 winning captain Lasith Malinga (8 wickets), Zaheer Khan (8) and former captain Harbhajan Singh (2 wickets with economical bowling) being the pick of the lot.
New Zealand's all rounder Corey Anderson has performed miserably with both bat and ball while spinner Pragyan Ojha has also been disappointing but will be happy to bowl on the Wankhede wicket that normally assists both spin and pace.
The trouble with MI is their bench strength is not great and they would be hoping that new inclusion Lendl Simmons of the West Indies justifies his signing. Punjab, on the other hand, are sitting pretty as the only unbeaten team in the league in the UAE leg.
For this top perch, they are indebted to Australian Glen Maxwell who has struck two brilliant 90s and another 89 to lead their batting might.
Maxwell (300 runs from 5 games) and David Miller (155) helped Punjab get a flying start in their opening two games against former two-time champions Chennai Super Kings and 2008 winners Rajasthan Royals.
When they failed later, Virender Sehwag has chipped in with two 30-plus scores in low-scoring games. Captain George Bailey, also a fine T20 batsman, has not been required to do much. They have, in short, a top-drawer batting order.
Australian pace spearhead Mitchell Johnson and Sandeep Sharma have opened the bowling well and have got good support from the experienced L Balaji and Rishi Dhawan.
But the spin department appears a bit stretched with young left arm spinner Akshar Patel impressing with his wicket taking (6 wickets) ability and economy though former India bowler Murali Karthik, who has been benched in four games, has more experience.
By Bharat Sundaresan