The 2016 season saw the Rams attempting to improve upon their 7–9 record from 2015. After a surprising 3–1 start, the Rams would massively struggle in the second half, going 1–11 in their final 12 games, en route to a 4–12 record. The Rams also went 1–6 at home in 2016, their worst home record since going 0–8 at home in their 1–15 2009 season. The Rams also missed the playoffs for the 12th straight season, the third longest current streak in the NFL. Only the Buffalo Bills and Cleveland Browns had longer postseason droughts. The franchise also clinched its 13th straight losing season, which as of 2017 was the longest current streak in the NFL. The Rams were also the only team to lose to the San Francisco 49ers in 2016, as both wins for the 49ers were against the Rams.
On December 12, 2016, Fisher was fired after a 42-14 loss to the Atlanta Falcons that dropped the Rams to 4-9 and clinched their 10th straight losing season. John Fassel was named interim head coach and went winless over the final three games.
The Rams competed against the San Diego Chargers and Oakland Raiders, both of whom also filed relocation requests for a joint stadium in Carson for the rights to the Los Angeles market; the Chargers received a one-year option to decide if they wanted to share the Inglewood stadium with the Rams, which they did in the following season in 2017. Had the Chargers not accepted the option, a one-year option would have been granted to the Raiders after theirs expired. The league made their decision in a special meeting on January 12; after two ballots, the Rams' proposal was accepted on a 30–2 vote.
The Rams' return to the Greater Los Angeles Area received extensive media coverage. The team made its first appearance on HBO's Hard Knocks, which covered training camp and preseason. Several players and their families were followed on the new E! reality series Hollywood & Football as they settled in Southern California, while the regular season was later chronicled in the Amazon Prime sports documentary series All Or Nothing.
The Rams acquired the No. 1 overall pick from the Tennessee Titans along with a 4th and 6th round selections in exchange for the Rams No. 15 overall pick, two second-round picks, and a third-round pick in the 2016 draft. The Titans also received the Rams first and third-round picks in 2017.
The Rams acquired an additional second-round selection as part of a trade that sent quarterbackSam Bradford to the Philadelphia Eagles. This selection along with their original second-round pick were traded for the number one overall selection of the 2017 draft.
On November 25, 2015, the NFL announced that the Rams would play host to a then-undetermined NFC East opponent in the International Series, in the first-ever game at Twickenham Stadium in London, United Kingdom. On January 3, 2016, the New York Giants were confirmed as the Rams' opponent for this game, both teams having finished in third place in their respective divisions in the 2015 season. The game was played in Week 7 on Sunday, October 23. The kickoff time was announced on April 14, and both teams had their bye the following week. As a condition of the Rams' use of the Coliseum, the University of Southern California requested that the NFL not schedule any Monday night home games at the stadium, nor any home games on days after USC football games. While the team's final schedule did not contain any home Monday night games, two games were played on days following an USC home game. The Rams wore their white uniforms for all of their home games for the first time since 1971 as a nod to the Fearsome Foursome era, with the exception of wearing their throwback uniforms twice a year for home games and wearing their all-navy uniforms for the game in London.
With the win, the Rams won a regular season game in Los Angeles for the first time since 1994. They paid tribute to their first regular season game back in Los Angeles by wearing their throwback uniforms, which were their uniforms in their last season in 1994.
LA – Tavon Austin 43-yard pass from Case Keenum (run failed), 3:39. Rams 37–26. Drive: 7 plays, 75 yards, 4:17.
TB – Mike Evans 7-yard pass from Jameis Winston (pass failed), 2:24. Rams 37–32. Drive 11 plays, 75 yards, 2:23.
LA – Case Keenum – 14/26, 190 yards, 2 TD, INT
TB – Jameis Winston – 36/58, 405 yards, 3 TD, INT
LA – Todd Gurley – 27 rushes, 87 yards, TD
TB – Charles Sims – 13 rushes, 55 yards, TD
LA – Tavon Austin – 5 receptions, 82 yards, TD
TB – Mike Evans – 10 receptions, 132 yards, TD
In what was a game that pitted both teams offenses and defenses together, the Rams won 37–32 with their defense securing the victory at the end of the game and scoring at least 5 touchdowns. With the win, the Rams record improved to 2–1 for the first time since 2006, placing the team in first place in the NFC West. It was also the first time the Rams scored a regular season touchdown as the Los Angeles Rams since 1994.
Case Keenum set a team record with 19 straight completions. He finished the game with 321 passing yards and four total touchdowns. With the game tied at 28, Matt Prater booted a field goal to lead Detroit 31–28. Keenum's day was ruined as his pass intended for Lance Kendricks was intercepted at the last second by the Lions, who would eventually win the game 31–28.
After scoring 10 points on their first two drives, the Rams could not score again as they allowed 17 unanswered points with a field goal, a pick 6 by Landon Collins, a 1-yard touchdown by Rashad Jennings. Case Keenum threw 4 interceptions in the game. One of the picks was on the last drive when the Rams drove down to the red zone. But a high pass landed in DRC's hands in the end zone allowing the Rams to drop 3–4 and continue on their losing streak.
With the win, the Rams improved to 4–5 without scoring a touchdown. This game was the Rams' only win in a series of 12 games, and their last win of the 2016 season, as they would go on to lose their remaining 7 games.
This game was the first time rookie quarterback Jared Goff made his starting debut for the Rams. The Rams held a 10–0 lead with just over 4 minutes left to play; however, the Dolphins would score 14 unanswered points to take a 14–10 win. With the loss, the Rams fell to 4–6.
With the loss, the Rams were mathematically eliminated from postseason contention. This is Jeff Fisher's last game as the Rams' head coach before getting fired the next day. Todd Gurley after the game lashed out at the team for having a "middle-school offense."