The unbeaten welterweight has been in the frame for a title shot for over a year but saw a fight with IBF champion Devon Alexander fall through three times due to injuries to both men.
Brook now hopes to secure a fight with the winner of Alexander's November 30 defence against Shawn Porter after an exciting performance which saw him knock Senchenko down twice - but get hurt himself too - at the Motorpoint Arena.
Brook's only other fight in 2013 was a comfortable win over Carson Jones in July. He found himself needing to win this IBF title eliminator against Senchenko despite having previously been made mandatory challenger for the belt.
Ukrainian former world champion Senchenko has been similarly inactive, fighting only once since ending Hatton's career with a ninth-round stoppage last November.
The veteran still harboured ambitions to win another world title himself but was up against it against the Sheffield man.
A cagey first round saw Brook stalk his man without landing much of note.
Senchenko, much the taller man, landed a couple of left hooks in the second but a right over the top from Brook was nicely delivered.
The fight ignited in the third. A right hand bloodied Senchenko's nose and had him hurt. Brook had the fire in his belly and built on his success, flooring Senchenko hard with a booming right cross.
Senchenko got up quickly but was up against it, Brook landing a hooking right to the head. Brook remained composed - but vicious - and had the Ukrainian reeling across the ring before landing a two hurtful uppercuts before the bell.
Brook was hurt in the fourth as his legs went to jelly very briefly after a nice right but he recovered well.
Indeed it was Senchenko who went down, Brook timing his jabs perfectly before a savage right hand and glancing uppercut had Senchenko down again. He again rose to his feet, but was on very unsteady legs as the fight was waved off.
On the undercard, Olympic super-heavyweight champion Anthony Joshua continued his professional apprenticeship with a destructive second-round stoppage win over journeyman Paul Butlin.
The Londoner beat Emanuele Leo comfortably with a first-round stoppage earlier this month and was obviously expected to make it two wins from two against Melton Mowbray's Butlin.
He did that in style, dominating the first round before forcing the technical knockout by putting Butlin down in the second and prompting the referee to end it.
Blackpool's Brian Rose controversially won his WBO light-middleweight title final eliminator against Argentinian Javier Maciel despite the majority in attendance seeing the away fighter as the clear winner.
Rose was hurt and bloodied early on and looked second best for much of the fight but took a split decision win with scores of 115-113 to Maciel and 116-113 and 117-111 to Rose - the latter tally frankly ludicrous.
Brook, whose record now reads 31-0 with 21 early wins, said afterwards: "I believe I've made a statement here.
"When I hurt him I knew I could take my time. I nearly got lackadaisical and I got caught myself, but I thought 'I'm going to get you back for that'.
"I wasn't really hurt, it was just a bit of a buzz. But I'm fit and healthy and felt great tonight.
"I'm glad to have got revenge for Ricky."
Senchenko drops to 33-2 (23KO wins).