The winter of 1980-81 was disrupted by the outbreak of open hostility between the FISA and the FOCA. The result was that the South African GP on February 7 featured only the FOCA teams. This was won by Carlos Reutemann in a Williams FW07B but in the end it did not count for points. Goodyear had decided to withdraw from F1 and so everyone was on Michelin tyres when the 29 cars appeared at Long Beach.

There had been a lot of change over the winter. Williams was the same as before with World Champion Alan Jones and Reutemann and Brabham was little-changed as well with BT49Cs for Nelson Piquet and Héctor Rebaque. McLaren had lost Alain Prost to Renault, despite a two-year contract and so John Watson was partnered by Andrea de Cesaris. The team was in the process of being taken over by Ron Dennis's Project 4 and one of the new all-carbonfiber cars appeared in practice. Jean-Pierre Jabouille was still not recovered from his leg injuries from Canada the previous autumn and so his place in the Ligier team (now called Talbot and using the old Matra V12 engines again) and so Jean-Pierre Jarier was called in to be Jacques Laffite's team mate. Tyrrell had lost both of its 1980 drivers with Derek Daly moving to March and so hired Eddie Cheever and Kevin Cogan. The team was without sponsorship again.

Ferrari had replaced the retired Jody Scheckter with Didier Pironi and the team had the new turbocharged 126CK. Team Lotus had lost Mario Andretti to Alfa Romeo and so had hired Nigel Mansell to partner Elio de Angelis and debuted the controversial twin-chassisLotus. Team Ensign struggled on with Marc Surer driving while Emerson Fittipaldi had finally decided to retire as a driver and had hired Chico Serra to partner Keke Rosberg. Arrows had new sponsorship from Ceramiche Ragno and Beta and was running Riccardo Patrese and new boy Siegfried Stohr while Osella has expanded to two cars for Miguel Ángel Guerra and Beppe Gabbiani. ATS continued with one car for Jan Lammers, while Theodore Racing had produced a new chassis for Patrick Tambay and RAM had gone into business with March Engineering and was running two March 811s for Daly and Eliseo Salazar.

Qualifying resulted in something of a surprise with Patrese on pole in the Arrows with Jones and Reutemann behind him. Piquet was fourth with Villeneuve fifth, Andretti sixth and Mansell seventh. The top 10 was completed by Cheever, Giacomelli (Alfa Romeo) and Jarier.

At the start Villeneuve made an amazing start and charged down to the first corner so quickly that he overshot and so Patrese went into the lead with Jones and Reutemann chasing. In the middle of the pack Prost and de Cesaris collided and both went out. Pironi made a remarkable start to go from 11th on the grid to fourth, ahead of Piquet, the recovering Villeneuve, Cheever and Andretti. On the second lap Reutemann overtook Jones for second but otherwise the top six remained unchanged until lap 17 when Pironi was able to pass Piquet for fourth but on the next lap Villeneuve's Ferrari stopped with a driveshaft failure and so Cheever moved to sixth place. On lap 25 Patrese began to suffer from fuel pressure problems and lost the lead to Reutemann. Patrese soon headed for the pits and so everyone moved up a place and Andretti took over sixth place. As Jones closed up on Reutemann, the Argentine driver made a mistake as he lapped Surer and went wide. Jones went ahead. On the same lap Laffite overtook Andretti for sixth place and chased after Cheever. The two cars collided on lap 41 and Laffite ended up in the pits. As Cheever began to drop back, Andretti was able to climb to fifth place and on lap 54 that became fourth when Pironi slowed with an oil leak.

Jones thus led another Williams 1-2 with Piquet third, Andretti fourth, Cheever fifth and Tambay sixth in the Theodore.