After a relatively slow start, Gayle upped his tempo as he scored his 92 off just 58 deliveries and hit 11 boundaries and five towering sixes in the process.
Gayle initially adopted a wait and watch policy on a seaming Chinnaswammy track before exploding in the eight over.
Even though wickets kept tumbling at the other end, the big-hitting West Indian was hardly bothered as he went about his business in style, notching up his 13th IPL fifty and first of the season.
Newly-appointed RCB captain Virat Kohli played a short 24-run cameo before he was LBW by debutant Jasprit Bumrah, who returned with the best figures for the Mumbai outfit scalping three wickets for 32 runs.
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Bumrah, with a unique action, then accounted for Mayank Agarwal in his next over caught by Sachin Tendulkar.
With wickets falling at the other end, it took Gayle eight overs to broke his shackles when he cracked a boundary and a six off Bumrah in consecutive balls.
After opening up, Gayle then targeted his West Indian team-mate Kieron Pollard, picking up 15 runs with two boundaries and a six off the 11th over
Out-of-favour India off-spinner Harbhajan Singh gave Mumbai a much-needed breakthrough in the form of Daniel Christian, caught at deep midwicket by Johsnson.
Bumrah scalped his third wicket when he trapped Karun Nair leg before to see RCB in a spot of bother a 80 for four in 12.4 overs.