Nikolic opened the scoring for the hosts in the 15th minute, heading home from a pinpoint Brandon Vincent cross to put his team up 1-0.
David Accam was in the right place at the right time for Chicago's second, the Fire striker found himself alone and blasted home from the far post following a slick team move in the Colorado penalty area.
The Fire's offseason acquisition added his second in the 74th minute from a perfectly weighted Michael de Leeuw pass that beat three Colorado defenders and goalkeeper Tim Howard for Nikolic to slot home to seal the win for Chicago.
The goals were Nikolic's ninth and 10th of the season, giving him two more than Erick Torres for the overall lead in goals so far in 2017.
Gerso Fernandes scored three second-half goals in 13 minutes, Tim Melia had his seventh shutout and Sporting Kansas City beat the Seattle Sounders 3-0 for sole possession of first place in the Western Conference.
Kansas City is undefeated in 15 straight home games, while Seattle lost its third straight.
Gerso is the first Sporting KC player with a hat trick since Birahim Diop in 2010. In the 56th minute, Gerso had a deflected corner kick fall to his feet and he slotted it inside the near post.
Two minutes later, Gerso put a first-time shot off the post and then put it home after blocking a clearance attempt. In the 69th, Graham Zusi found space along the edge of the 18-yard box and found his teammate open at the penalty spot for his third.
Melia kept it scoreless in the first half with two quality saves just before half-time. He stayed low to kick away Alvaro Fernandez's breakaway shot in the 45th and on the ensuing corner kick, Melia dove to his left to deny Cristian Roldan's shot from distance.
Fabrice-Jean Picault and Ilsinho scored, Chris Pontius had two assists and the Philadelphia Union beat the Houston Dynamo 2-0 for their third-straight victory.
Philadelphia is unbeaten in five straight, with four straight shutouts by goalkeeper Andre Blake. Houston dropped to 0-4 on the road with just two goals, both coming in its first match against Portland.
Picault jumped through the center of the box to head Pontius' cross off the crossbar and into the net in the 17th minute. Ilsinho scored his first goal of the season in the 38th minute, sneaking through the center of the defense to beat goalkeeper Joe Willis from the penalty spot.
The Dynamo had a good scoring chance in the 40th minute, but Blake dove to his right to deny Mauro Manotas' breakaway shot.
Aaron Maund scored the go-ahead goal in the 51st minute asReal Salt Lake beat New York City FC 2-1 on a snowy night in Utah.
Real Salt Lake snapped a four-game losing streak, while NYCFC had its three-game undefeated streak snapped.
Albert Rusnak tied it at one for RSL in the 38th minute on Jefferson Savarino's first MLS assist. Savarino cut back his defender, rolled it across the top of the 18-yard box and Rusnak settled it for a shot from distance. Rusnak's corner kick in the 51st minute was headed in by Maund.
The visitors opened the scoring in the fourth minute -- NYCFC has now scored in 10 straight games. RSL's deflected back pass fell to Sean Okoli's feet and he dribbled between two defenders to the edge of the six-yard box for a sliding finish inside the far post. It was his first MLS goal.
Carlos Rivas scored in the 80th minute for Orlando City FC, and Chris Wondolowski tied it three minutes later for the San Jose Earthquakes as the clubs played to a 1-1 draw in Wednesday's late game.
Rivas' second goal of the season for Orlando City was assisted by Victor Pagliari Giro and Kaka. Wondolowski, who quickly answered for San Jose, was set up by Tommy Thompson. After receiving a caroming corner kick at the top of the box, Thompson found Wondolowski near the left goal post for the tying score.
Kaka broke free for a final scoring chance for Orlando City in the 90th minute, but San Jose goalkeeper David Bingham made the save to preserve the draw.
Scoring opportunities were sparse almost all night, with the teams combining for 29 total shots but just seven on target.
This was the third all-time meeting between Orlando City and San Jose, with each ending in a tie.
Chicago 3-0 Colorado: Nikolic makes his mark
The Chicago Fire were in dominant form from start to finish against a tepid Rapid's, and punished by lethal Nemanja Nikolic.
Sporting KC 3-0 Seattle: Gerso the difference
Gerso netted three goals in a 13-minute span to lift Sporting KC to a 3-0 victory over Seattle Sounders.
Philadelphia 2-0 Houston: Union win second straight
Two first-half goals were enough for the Philadelphia Union to secure their second-straight win in league play.
Real Salt Lake 2-1 NYCFC: Rusnak helps end skid
Goals from Albert Rusnak and Aaron Maund helped Real Salt Lake come back against NYCFC on a snowy night at Rio Tinto Stadium.