Guillaume Beuzelin grabbed a double as Hibs scored four second-half goals to complete a stunning comeback.
Simon Ford nodded Killie ahead after seven minutes, with James Fowler lashing in the second before the break.
Gary Caldwell's 20-yard drive pulled a goal back after 53 minutes, before Beuzelin's diving header made it 2-2 eight minutes later.
A second header from Beuzelin put Hibs ahead after 80 minutes, with Derek Riordan sealing the win a minute later.
Both sides were looking to continue impressive starts in the SPL this season as they lined up at Easter Road.
The home side launched their first attack seconds into the game when Garry O'Connor's pass met Derek Riordan out on the left and the striker squeezed an acute shot at goal, which fell just over the crossbar.
At the other end of the park, Gary Wales saw his header turned past the post.
However, the corner led to the breakthrough and Kilmarnock were ahead in the seventh minute.
Locke flighted a dangerous-looking ball into the box, Gordon Greer flicked it into the path of Simon Ford and the ex-Grimsby man left goalkeeper Zbigniew Malkowski with little chance with the header from close range.
Alan Combe then pulled off a great save to block O'Connor's header before Stephen Fletcher eventually managed to breach the goal, but the effort was ruled offside.
Instead, it was Kilmarnock who found the back of the net when Colin Nish completed some lovely build-up play by setting up Fowler for a thunderous finish four minutes before the break.
The Edinburgh side hauled themselves back into the game after 53 minutes when Riordan set up Gary Caldwell, who bulleted a long, low drive into the back of the net.
It was the spur they needed and the home side were back on level terms eight minutes later.
Riordan was the provider again and, this time, it was Beuzelin who left the net bulging with a superb diving header.
By now, Hibs were well on top and it was no real surprise when they surged into the lead with 10 minutes to go.
Substitute Ivan Sproule won a free-kick on the edge of the area after being tripped by Steven Naismith.
Kevin Thomson curled the ball into the box and found the head of Beuzelin who nodded home his second of the day from a few yards out.
Hibs were on a roll and added to their tally a minute later when Beuzelin's cross was met by Fletcher who nodded into the path of Riordan and he calmly fired home to secure the win.
Hibernian: Malkowski, Whittaker (Rudge 52), Caldwell, Hogg, Glass, Fletcher, Beuzelin, Stewart (Sproule 45), Thomson, O'Connor (Morrow 76), Riordan. Subs Not Used: Simon Brown, Konte, Shiels, Stevenson.
Booked: O'Connor, Riordan, Glass, Thomson.
Goals: Caldwell 53, Beuzelin 61, 80, Riordan 81.
Kilmarnock: Combe, Fowler, Ford, Greer, Hay, Johnston, McDonald, Locke, Invincibile, Nish (Naismith 64), Wales (Boyd 64). Subs Not Used: Smith, Lilley, Dodds, Dillon, Campbell.
Booked: Nish, Naismith, Hay.
Goals: Ford 7, Fowler 40.
Ref: A Freeland