Batting first, Mumbai scored a stiff 178 for three riding on half-centuries from Lendl Simons (62) and Mike Hussey (56).
In reply, Royals were never in the chase as they were restricted for 153 for eight. Karun Nair with 48 off 24 balls was the lone ranger for the Royals. Brad Hodge (40) and James Faulkner (31) tried their bit but it was too late by then.
It was a collective effort by the MI bowlers led by senior pro Harbhajan Singh, who outshone others with brilliant figures of two for 13 from four overs. Pragyan Ojha also did his bit with two for 30 from his four overs.
Royals' team management's baffling decision to rest the performing trio of Ajinkya Rahane, Pravin Tambe and Steven Smith backfired as the team lost the necessary momentum going into the match.
Royals with 14 points from 12 games remain third in the table and firmly in the hunt. But back to back losses will certainly affect their chances of finishing in the top two which would have given them an additional game.
Mumbai now have eight points from 11 matches.
Unmukt Chand (2) finally got a game but could well be the last one in the tournament. It was a rank bad delivery from Pragyan Ojha and Unmukt failed in his bid to play a proper pull-shot as Mike Hussey made no mistake at the deep mid-wicket boundary.
Shane Watson (5) did not get going as he misjudged the turn off an Ojha delivery and the ball ballooned up hitting the toe-end of the bat for Ambati Rayudu to take a simple catch at mid-on.
Sanju Samson (2) also played early to a Krishmar Santokie slower as Rayudu got his second catch as Royals were reduced to 42 for three.
While Karun was playing his strokes at other end, Kevon Cooper was dismissed by a sheer piece of fieldingÂ brilliance from Kieron Pollard standing at the long-on boundary. Cooper hit a Harbhajan delivery which would have been a sure six had any other fielder save Pollard manning that area.
The giant Caribbean timed his jump to perfection as he plucked a one-handed catch but the momentum was forcing him over the ropes. He kept his balance and threw the ball inside. He then turned in a flash to dive in front and completed a stunner as Cooper looked shell-shocked.
At 61 for four, leggie Shreyash Gopal playing his first game was brought into operation. He accounted for Ankit Sharma and Stuart Binny in quick succession to ensure that there was no comeback for the Royals.
Karun's fight ended when he was holed out off a Harbhajan Singh delivery caught by Krishmar Santokie.
At the end of 12 overs, Royals were reeling at 75 for seven. Faulkner and Hodge did try but there was too much to do in the end.
Earlier, Mumbai Indians top-order fired in one of the rare occasions as they put up a competitive 178 for three due to a century-plus opening stand between Mike Hussey and Lendl Simons.
Comeback man Hussey (56) and Simons (62) put on 120 runs for the opening stand, which incidentally was the first three-figure partnership for MI in 30 games.
The last time MI had a century stand was when Sachin Tendulkar and Dwayne Smith conjured 163 runs against the same opposition during the 2012 edition.
Hussey scored his runs in 39 balls with three fours and two sixes while Simons took 51 balls, which included six fours and two sixes.
Skipper Rohit Sharma showed his big-hitting prowess during a 19-ball cameo that fetched him 40 runs with three fours and four sixes. Rohit and a subdued Kieron Pollard (14 no) added 56 for the third wicket in five overs.
Hussey and Simons started cautiously trying to get a measure of the slow Motera track. Hussey, coming back to the team after a disastrous UAE leg, looked confident as he played some fluent drives and cuts peppering the in-field. Simons also proved to be an able partner as he started slowly but picked up the pace as time progressed. Both ran well between the wickets converting a couple of singles into twos.
MI's opening stand yielded 50 runs in 6.4 overs with Simons racing to 30.
When Faulkner dropped one short, Hussey was quickly on backfoot to pull it in front of square for a six.
Hussey's second six was a slog sweep off left-arm spinner Ankit Sharma into the mid-wicket stands.
Simons also joined the fun as he lofted an ultra-slow delivery from Rajat Bhatia into the deep mid-wicket stands while lofting Kevon Cooper over long-off for his second six.
Hussey was the first to reach the half-century of 32 balls while Simons took 43 balls to attain the individual landmark.
Their 100-run partnership, MI's first of the season came in the 13th over.
Royals drew the first blood immediately after the second strategic time-out as Ankit got both Simons (62) and Hussey (56) within a space of two deliveries--- both caught in the deep by Cooper.
Ankit ended with impressive figures of two for 23 in four overs.