Fisher was the team's coach since 2012, and compiled a 31-45-1 record with the Rams. He oversaw the move from St. Louis to Los Angeles this past offseason.
The lack of success on the field, capped by a 42-14 home rout at the hands of Atlanta on Sunday, spelled the end for Fisher, who tied Dan Reeves with 165 career reguklar-season defeats. That's the most in league history, and Fisher has the lowest winning percentage (.512) among coaches with 130-plus losses.
Los Angeles is 4-9 this season and has scored a league-low 194 points.
"Making a decision such as this, especially during the season, is one of the most difficult in sports," Rams owner Stan Kroenke said.
"I have great respect for Jeff as a coach, person, father and friend. He has worked tirelessly despite some challenging circumstances. He played an integral role in helping this team make history in returning the NFL to Los Angeles, and we always will be grateful for his commitment and dedication to our organization."
Fisher, 58, went 147-126 as coach of the Houston Oilers/Tennessee Titans and helped that franchise in its relocation. He led the Titans to the 1999 AFC championship.
Long respected in league circles for his work on the NFL's competition committee, Fisher never found success — or a franchise quarterback — with the Rams, who went 7-8-1, 7-9, 6-10 and 7-9 in his four full seasons.
They traded up for the first selection in this year's draft and took Cal's Jared Goff, but he rode the bench for much of the season behind journeyman Case Keenum as LA started the schedule 3-1. Fisher finally turned to Goff in Week 11 and the Rams dropped all four of his starts.
Kroenke said in his statement that "this is the right time to make a change as our performance has not lived up to my or our fans' expectations. We all are focused on improving as an organization and building a team that makes Los Angeles proud. Our mission is to celebrate a Super Bowl title with our fans in Los Angeles. Today is the first step to bringing us closer to that goal."
Oddly, Kroenke gave Fisher a contract extension before the season, though it was not made public until recently.
Now, that extension looks more like a bonus to Fisher for his role in aiding the organization's move to California than being any part of a plan for the team's future.
Attendance has been something of an issue at the Los Angeles Memorial Coliseum, which has a listed capacity of 93,607. Only in their home opener did they approach that number, and they drew 82,495 on Sunday.