Coming back into the team, young leg-spinner Sandeep Lamichhane returned figures of 3/40, playing an influential role in helping DC rally after Gayle's blitzkrieg.
Considering the dew factor in mind, Delhi Capitals skipper Shreyas Iyer invited the visitors to bat first.
And the hosts, seeking to end their run of woes at the Feroz Shah Kotla, enjoyed early success when Lamichhane tossed the ball up and had K L Rahul stumped with one that turned sharply in the second over.
Rishabh Pant did a fine job whipping the bails off in a flash, as Rahul walked back after welcoming Lamichhane with a six down the ground and a four.
Apart from managing two runs from the nine deliveries he faced, Mayank Agarwal watched the action unfold from the other end, as Gayle flayed the Delhi spinners.
The 'Universe Boss', entering the game with 421 runs from nine matches, started his onslaught by smashing Ishant Sharma's knuckleball over long on for one of the biggest sixes the stadium has ever witnessed, the 101m maximum threatening to break the windows of The Willingdon Pavilion.
He toyed with Amit Sharma and smoked the experienced leg-spinner for three maximums, including two over the deep mid wicket region.
Before that, the big-hitting Jamaican, one of the biggest globetrotters in T20 leagues, cut, drove and swept Lamichhane for four boundaries in a single over.
It took an acrobatic effort from Colin Ingram in the deep to bring to an end Gayle's belligerent stay in the middle. After sweeping a Lamichhane delivery into the crowd, Gayle went for one too many, and Ingram, taking the ball over his head, lobbed it to Axar Patel before falling on the other side of the rope.
Returning to the playing XI, Lamichhane dismissed Sam Curran in the same 13th over in which he had Gayle, to peg the visitors back.
Pacer Kagiso Rabada picked up 2/23 in four overs, while Axar Patel took 2/22 in three overs.