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Berdych had caused the first major upset of the tournament when he ousted world number one Novak Djokovic on Friday.
However, despite an improved second set performance against the fifth seed, the Czech could not match Nadal's power as the Spaniard put himself within touch of a second title inside a week following his Madrid Masters triumph last Sunday.
Berdych had beaten Djokovic on Friday with a combination of big serves and smart shots from the middle of the second set.
But the big Czech was given little chance by six-time champion Nadal, who after back-to-back three-set matches looked keen to get this semi-final over and done with as quickly as possible.
Nadal, who has now reached eight finals in as many events since his return from a seven-month injury lay-off, broke Berdych twice in the opening set, including in the opening game.
Berdych's chances of victory looked slim considering the statistics - he had beaten Nadal only three times in their 16 previous encounters. Only four of those were on clay, and all were won by the Spaniard.
Berdych started the second set positively by holding serve, but squandered his first break point in the next.
This was a much tighter set, but Berdych's slim hopes were tempered by a Nadal forehand winner in the ninth game which gave him the break.
The Spaniard sealed the win in the 10th game when Berdych sent a backhand return beyond the baseline.
Nadal will meet Federer on Sunday if the Swiss second seed beats French upstart Benoit Paire in Saturday's second semi-final.
Nadal will be looking for a 24th Masters title on Sunday.
Results on the seventh day of the ATP Rome Masters/WTA Rome Open on Saturday (x denotes seeding):
Men
Semi-finals
Rafael Nadal (ESP x5) bt Tomas Berdych (CZE x6) 6-2, 6-4
Playing later:
Benoit Paire (FRA) v Roger Federer (SUI x2)
Women
Semi-finals
Serena Williams (USA x1) bt Simona Halep (ROM) 6-3, 6-0
Victoria Azarenka (BLR x3) bt Sara Errani (ITA x7) 6-0, 7-5
