Lincoln went two goals ahead in the first half hour but then had central defender Danny Hone red-carded early in the second half.
But Chesterfield failed to take advantage of the extra man and went further behind before getting a late consolation goal.
Lincoln went in front after 18 minutes after a controversial decision by referee Michael Jones, who ruled that Kevin Austin had fouled Paul Green just outside the box.
Stefan Oakes fired the resulting free-kick straight through the crowded penalty area and into the bottom corner.
Three minutes later, Chesterfield were almost caught out again when a cross from Lenell John-Lewis found Adrian Patulea on the edge of the six-yard box.
The Romanian striker had his back to goal but sent in an overhead kick which beat Chesterfield keeper Trevor Carson but struck the bar and Rob Page cleared.
But Lincoln were not to be denied and in the 29th minute John Lewis broke through three tackles inside the box.
His shot was only pushed out by Carson and Patulea pounced to score his fourth goal of the season.
Chesterfield's frustration began to show with both Paul Harsley and Lloyd Kerry shown yellow cards before manager Lee Richardson was sent to the stands for complaining about the referee as the teams left the pitch at half-time.
Chesterfield looked to have been given a lifeline in the 47th minute when Hone received a straight red card for wrestling Jack Lester to the ground when the striker was clear.
But even with 10 men, Lincoln created chances and they got their third goal after 55 minutes.
Scott Kerr fired in a cross from the edge of the box and the Chesterfield defence allowed Janos Kovacs to steal in at the far post and head home.
Lincoln were forced to defend in depth as Chesterfield poured men forward.
The Spireites pulled a goal back in the 73rd minute but Lincoln sub Frank Sinclair gave the ball away just outside his own box and Lester fired in.
Chesterfield went close again nine minutes from time when Jamie Ward smacked a shot against the crossbar.
Then Lester got into a good position but Lincoln were saved by a last-ditch tackle from Lee Beevers.