Braces from former Liverpool player Xherdan Shaquiri and Maren Haile-Selassie sealed a 4-1 win for the hosts over the Herons, who once again found themselves without star, Lionel Messi.
Making the playoffs was already an uphill battle for Miami but the defeat leaves the task almost impossible.
However, Tata Martino’s side does emerge from the defeat still mathematically alive in the Eastern Conference playoff chase but must win its remaining games as well as rely on help elsewhere if it is to cling on to the hope of making the postseason.
Josef Marinez recorded the lone goal for Miami (9-16-6, 33 points), which was without Messi for the fourth straight match across all competitions. The Argentine superstar has one goal and two assists in MLS regular-season play, but he has not taken the field since a Sept. 20 meeting with Toronto FC.
With the win, Chicago (10-12-10, 40 points) moved above the playoff line into eighth in the Eastern Conference. Chicago also improved to 6-3-7 at home.
The loss drops Inter Miami to 3-11-2 in away matches this season, and they sit in 14th place in the 15-team East, five points below the playoff line.
Shaqiri scored in the 49th minute with a left-footed strike off a cross from Fabian Herbers.
Miami quickly responded in the 53rd minute. Chicago midfielder Jonathan Dean was assessed a yellow card for a handball in the penalty area. On the ensuing penalty kick, Martinez beat Fire goalkeeper Chris Brady to level the match.
Haile-Selassie replaced Brian Gutierrez as a second-half substitution in the 55th minute and made his presence felt immediately.
In the 62nd minute, Haile-Selassie restored Chicago’s lead, taking a through ball from Herbers and beating Inter Miami goalkeeper Drake Callender with a right-footed strike.
Then, four minutes later, the Swiss midfielder put a cross past a diving Callender for his sixth goal of the season.
Shaqiri gave Chicago a three-goal lead, striking a Gaston Gimenez feed past a diving Callender in the 73rd minute.
Braces from Xherdan Shaquiri (above) and Maren Haile-Selassie sealed the win for the hosts
Shaqiri scored in the 49th minute with a left-footed strike off a cross from Fabian Herbers
Haile-Selassie (pictured left) restored Chicago’s lead, taking a through ball from Herbers
The two sides played to a scoreless first half. Despite Miami controlling the possession, it was Chicago with the better opportunities.
Gimenez had a glorious chance in the sixth minute but put his strike over the bar.
Miami’s best chance came in the 23rd minute with DeAndre Yedlin at the side of the goal, but the Miami defender couldn’t get enough on his strike to put it on target.
Chicago’s best opportunity came before the first half whistle when Georgios Koutsias’ strike deflected off Miami defender Sergii Kryvstov and hit the post.