The 42-year-old - making his debut at the season-ending tournament that year - went on to reach the final, where he lost to Roger Federer in three sets. Blake faced a tough first match against Nadal but came up trumps in straight sets.
In a lung-bursting baseline exchange, the duo exchanged a series of bruising groundstrokes - 28 to be precise - before Blake crushed a crosscourt backhand winner.
The American replied to a video of the rally shared by Tennis TV by saying he was still "catching" his breath from that point.
"I'm still catching my breath from this point," Blake tweeted.
Blake followed up his win against Nadal with another against Nikolay Davydenko. Although he lost his last round-robin match to Tommy Robredo in three sets, the American qualified for the semifinals. There he beat David Nalbandian to book a meeting with Federer.
The then World No. 8, though, ran out of steam in the final, as Federer dropped only seven games - including a bagel set - to cruise to the title. Nadal, meanwhile, lost to Federer in the last four.
Rafael Nadal qualifies for 2022 ATP Finals
Rafael Nadal is still going strong at the age of 36. He started the year with a second triumph at the Australian Open - becoming the first male player to win 21 Grand Slam singles titles.
The Spaniard would go 20 matches unbeaten on the year - winning three titles - before losing to Taylor Fritz in the Indian Wells final. Making a belated start to his claycourt campaign due to injury, Nadal endured early defeats in Madrid and Rome before winning a record 14th Roland Garros title.
Playing competitively for the first time on grass, Nadal reached the Wimbledon semifinals before withdrawing because of an abdominal tear. After losing on his return at Cincinnati, the Spaniard reached the US Open fourth round, losing to Frances Tiafoe.
Nevertheless, that run made Nadal the first player to qualify for the season-ending ATP Finals in Turin.
The Spaniard made a lone doubles appearance alongside Roger Federer at the Laver Cup last month. The legendary pair squandered a match point on the Federer serve to go down to Jack Sock and Frances Tiafoe.
Rafael Nadal hasn't yet confirmed his participation at the upcoming Paris Masters but is expected to make his 17th appearance at the ATP Finals.