The MP4/6 was the first McLaren chassis to use a Honda V12 engine, which Honda rated at 735 PS (725 bhp) at 13,500 rpm. Initial impressions from both Berger and Senna during pre-season testing were lukewarm: both drivers felt the new V12 offered little advantage over the V10 unit used in the 1990 MP4/5B. Honda and McLaren responded with an intensive development programme, and by the latter half of the season the engine had been pushed to approximately 780 hp at 14,800 rpm.
A defining technical characteristic of the MP4/6 was its conventional "H"-pattern manual gearbox. A semi-automatic transmission was evaluated during the season and briefly shown at the Hungarian Grand Prix, but Senna's early off-track excursion on its only track outing ended development. The car was converted back to a manual gearbox and the semi-automatic unit never appeared in a race. Ferrari and Williams were the only teams to use semi-automatic gearboxes in 1991, leaving the MP4/6 as the last championship-winning car with a fully manual transmission.
Senna dominated the opening of the championship, winning the first four consecutive Grands Prix in the United States, Brazil, San Marino, and Monaco. McLaren's early advantage owed as much to the unreliability of the Renault V10-powered Williams FW14 as it did to the MP4/6's outright pace. Once Williams resolved their reliability issues, Nigel Mansell and the FW14 became the dominant force in mid-season, demonstrating superior aerodynamic and technical sophistication.
Senna maintained his championship challenge through consistent podium finishes. At Senna's insistence, Honda accelerated their engine upgrade programme, while Oatley reworked the sidepods and aerodynamic package. Senna won in Hungary and Belgium before clinching his third and final Drivers' Championship at the Japanese Grand Prix, finishing second behind Berger in a result the team reportedly engineered as a gift to their Austrian driver. Senna then won the season finale in Australia, confirming McLaren's Constructors' Championship.
In all, the MP4/6 claimed eight Grand Prix victories and ten pole positions, accumulating 148 points. The car was widely regarded as the most competitive machine on the grid during the early part of the year, but the Williams FW14 ultimately proved more advanced in pure technical terms.
McLaren continued racing the MP4/6 in upgraded "B" specification for the first two rounds of the 1992 season. Senna took a third-place finish in South Africa before the MP4/6B was retired in favour of the MP4/7A, which introduced a semi-automatic transmission and traction control. Three MP4/6B chassis were nonetheless brought to the 1992 Brazilian Grand Prix as spares.
The MP4/6 marked the end of the partnership era between McLaren and Honda that had begun with the MP4/4 in 1988. During that period, the partnership yielded four consecutive Constructors' Championships and three Drivers' titles for Senna. After 1992, McLaren switched to Ford engines and Honda departed Formula One.
The MP4/6 occupies a singular place in Formula One history: it was the last car to win the championship using a manually operated gearbox, a technology that would be permanently displaced by semi-automatic paddle-shift systems from 1993 onward. It also stands as the only V12-powered car to claim the Drivers' Championship in the modern era, since the shift toward V10 and subsequently V8 engines eliminated the V12 configuration from competition.
In the sim racing world, the MP4/6 has been preserved as a playable classic car in Codemasters' F1 series from F1 2017 through F1 2020, allowing modern drivers to experience the distinctive combination of Honda V12 power and manual shifting. It also appears in Automobilista 2, where it is bundled with the MP4/7A and MP4/8 in a McLaren classics pack.