The former Liverpool midfielder struck a sweet 20-yard volley in the 37th minute after United had dominated the opening stages.
Striker Leon Clarke should have scored with an early header and narrowly missed tapping in a cross from the lively Mark Duffy, before Spearing, then later booked, fired in his first goal since last February.
Both sides kicked off the season with new managers; Phil Parkinson for Wanderers and one-time Bolton target, Chris Wilder, in charge of the Blades. And with nearly 4,500 visiting fans watching on this was not the start Wilder anticipated.
However, Bolton had not lost a home league game to their South Yorkshire visitors since 1977. And they nearly doubled their advantage but for goalkeeper George Long's fine save to keep out a Darren Pratley header after 64 minutes.
Parkinson's only disappointment was the early exit on a stretcher of skipper Pratley with a leg injury.
Report supplied by the Press Association.
Chris Basham (Sheffield United) wins a free kick in the attacking half.
Foul by Josh Vela (Bolton Wanderers).
Substitution, Bolton Wanderers. Liam Trotter replaces Jay Spearing because of an injury.
Delay over. They are ready to continue.
Corner,  Sheffield United. Conceded by Dean Moxey.
Attempt missed. Mark Beevers (Bolton Wanderers) right footed shot from the centre of the box is close, but misses to the left.
Substitution, Bolton Wanderers. Jamie Proctor replaces Gary Madine.
Foul by Mark Beevers (Bolton Wanderers).
Che Adams (Sheffield United) wins a free kick in the attacking half.
Substitution, Sheffield United. Stefan Scougall replaces Mark Duffy.
Substitution, Sheffield United. Che Adams replaces Matt Done.
Attempt missed. Josh Vela (Bolton Wanderers) right footed shot from the left side of the box is just a bit too high.
Attempt saved. Darren Pratley (Bolton Wanderers) header from the centre of the box is saved in the bottom right corner.
Attempt missed. Mark Duffy (Sheffield United) right footed shot from the centre of the box is close, but misses the top left corner following a fast break.
Substitution, Bolton Wanderers. Mark Davies replaces Chris Taylor.
Foul by Gary Madine (Bolton Wanderers).
Chris Basham (Sheffield United) wins a free kick in the attacking half.
Corner,  Sheffield United. Conceded by Mark Howard.
Attempt missed. Gary Madine (Bolton Wanderers) right footed shot from more than 40 yards on the right wing is high and wide to the left.
Attempt missed. Leon Clarke (Sheffield United) right footed shot from the right side of the six yard box is close, but misses to the right.
Attempt blocked. John Fleck (Sheffield United) right footed shot from outside the box is blocked.
Foul by Jay Spearing (Bolton Wanderers).
Mark Duffy (Sheffield United) wins a free kick in the defensive half.
Second Half begins Bolton Wanderers 1, Sheffield United 0.
First Half ends, Bolton Wanderers 1, Sheffield United 0.
Jay Spearing (Bolton Wanderers) is shown the yellow card for a bad foul.
Foul by Jay Spearing (Bolton Wanderers).
Chris Basham (Sheffield United) wins a free kick on the right wing.
Corner,  Bolton Wanderers. Conceded by Jack O'Connell.
Attempt missed. Gary Madine (Bolton Wanderers) header from the right side of the six yard box is close, but misses to the right.
Leon Clarke (Sheffield United) is shown the yellow card for a bad foul.
Dean Moxey (Bolton Wanderers) wins a free kick on the right wing.
Foul by Leon Clarke (Sheffield United).
Goal!  Bolton Wanderers 1, Sheffield United 0. Jay Spearing (Bolton Wanderers) right footed shot from the centre of the box to the bottom right corner.
Josh Vela (Bolton Wanderers) is shown the yellow card for a bad foul.
Foul by Josh Vela (Bolton Wanderers).
John Brayford (Sheffield United) wins a free kick in the attacking half.
Attempt saved. Darren Pratley (Bolton Wanderers) right footed shot from outside the box is saved in the bottom left corner.
Foul by Leon Clarke (Sheffield United).
Darren Pratley (Bolton Wanderers) wins a free kick in the attacking half.
Jay Spearing scored the only goal as Bolton began life back in English football's third tier with a 1-0 win over Sheffield United.