The Silver Arrows have won the past seven constructors' championships and also gone away with the drivers' title on each occasion, including six wins for Hamilton – who also triumphed once with McLaren.
Both streaks are under threat in 2021, however, as Max Verstappen holds a 12-point advantage over Hamilton ahead of the Mexican Grand Prix on Sunday, while Red Bull is only 23 points back on Mercedes.
Toto Wolff, Mercedes' team principal, said: "The last race in Texas was more proof of just how intense this championship battle is.
"It's challenging, it's pushing both teams to higher levels, and the positive pressure we're putting on ourselves is making this a hugely enjoyable fight. We wouldn't have it any other way."
It is Red Bull who have the momentum, though, after Verstappen claimed a precious win in the United States.
"It was of course a great feeling to be back on the top step at the US Grand Prix," Verstappen said.
"The last few races were obviously quite difficult with various engine penalties and a few unlucky moments, so it definitely felt good to be back up there with Checo [Perez] beside me.
"It was a very satisfying win, we showed good pace at the US GP, so I'm looking to build on that momentum, and it was of course also very important to score solid points for the championship."
After Mexico, the teams head to Brazil and then Qatar before their next break, and Verstappen said: "I'm looking forward to it and I'm excited to get going, although I know the triple-header is going to be busy.
"It's incredibly important for myself and the team to try to nail the next three races now that we are fighting for the championship."
LAST TIME OUT
Verstappen won from pole in Austin, an event Mercedes had enjoyed great success at previously. It was not all plain sailing, though.
Despite starting from the front of the grid, the Dutchman was passed by Hamilton at the start.
With contrasting strategies, Red Bull called Verstappen in first for a pit stop as Hamilton stayed out, meaning he emerged behind his rival but with fresher tyres for a final push.
Mercedes promised their man the race would come down to the final three laps, and so it proved, but Hamilton failed to get within DRS range on the closing lap as Verstappen benefited from a tow off backmarker Mick Schumacher.
Verstappen held on as Hamilton's hopes of defending his title took another major hit.
WHAT TO EXPECT IN MEXICO
The big positive for Hamilton in Austin was the pace he had on offer, even if he ran out of laps with which to use it to his advantage.
The contrasting tactics helped in that regard, but Hamilton had also made a flying start, with his car clearly far more competitive now than earlier in the year when Red Bull dominated.
Both Hamilton and Verstappen have found joy previously in Mexico, so neither will be short of confidence, but the Briton must hope he has the opportunity to test his Mercedes again without this time having to make up such a significant deficit.
With little time to work on the cars between races across this double-header, the performances in Mexico should set the tone for a year-defining three weeks.
Verstappen is a long way from home in Mexico, but he and Red Bull should have the backing of a vocal crowd with Guadalajara native Sergio Perez in their second car.
TOP FIVE FACTS
Tight at the top – With five races remaining, 12 points represents the second-smallest gap between the top two in the hybrid era. Three points separated Nico Rosberg and Hamilton in 2014.
Standout season – Red Bull come into this race having celebrated nine wins this season, as many as in the previous three years combined. Their most victories were 13 in 2013.
Growing the gap – Hamilton might be second in the table this year, but he is way out in front all-time. Should he earn more points than Sebastian Vettel this week, his advantage over the second-placed Aston Martin man will increase to more than 1,000. Hamilton has 4,053.5, with Vettel on 3,054.
Failing from the front – Through Vettel and Charles Leclerc, Ferrari have taken two of the past three pole positions in Mexico. However, the Scuderia have not triumphed at this event since Alain Prost's win in 1990.
King of the continent – Hamilton has 17 wins in the Americas (seven in Canada, six in the US, two each in Brazil and Mexico), meaning he would surpass Michael Schumacher for the most of all-time with another. Of course, he failed in that respect in Texas.
1. Max Verstappen (Red Bull) 287.5
2. Lewis Hamilton (Mercedes) 275.5
3. Valtteri Bottas (Mercedes) 185
4. Sergio Perez (Red Bull) 150
5. Lando Norris (McLaren) 149
1. Mercedes 460.5
2. Red Bull 437.5
3. McLaren 254
4. Ferrari 250.5
5. Alpine 104