The first four-pointer featured a tremendous interchange between Lockyer and Lote Tuqiri.
A blistering performance sealed victory for Queensland over New South Wales in the first of this year's State of Origin series, in which Australian stars play for their home states.
An exciting opener in the best-of-three indicated a shift in the balance of power after the Blues' 3-0 whitewash last year.
An early second-half try from John Doyle on his debut knocked the stuffing out of New South Wales in front of 39,909 fans at Brisbane's Suncorp Stadium.
Two minutes earlier, Bryan Fletcher looked to have put them back in the game, driving over after some excellent running.
Inspirational
But a video replay showed he had lost his grip on the ball under pressure just before touching down. It was the Blues' second disallowed try.
Doyle turned provider for John Buttigieg on 49 minutes, as Queensland - transformed under coach Wayne Bennett - ran riot.
Inspirational first-time captain Gorden Tallis then set up another Maroons debutante, Chris Walker, for his first Origin try.
Queensland had their record Origin win, 36-6 in their sights, but the Blues fought back with two late tries.
Respectability
NSW got into double figures after skipper Brad Fittler intercepted and ran 60m for the Blues' second, which was converted by Michael de Vere for 34-10.
Trent Barrett added further respectability to the scoreline with a 72nd minute try, converted from under the posts for 34-16.
The Maroons were 16-4 ahead at the interval thanks to tries from Darren Lockyer, Darren Smith and Carl Webb.
The first four-pointer featured a tremendous interchange between Lockyer and Lote Tuqiri.
The latter took Lockyer's pass well inside the Queensland half and ran 60 metres before finding Lockyer on the inside to send him over.
The second try came courtesy of a nimble dummy and low drive for the line by Smith.
The third was provided by yet another Origin series first-timer as Webb showed great balance and footwork before shaking off three tacklers to score.
Before Webb's touchdown, Matthew Gidley had stepped outside Smith to go over for New South Wales.
The two disallowed Blues tries, one in each half, might have put a different complexion on the game.
But Queensland were always in charge and will go into the second game at Stadium Australia on 10 June full of confidence.