Nadal's astounding 50-set winning streak on clay came to an end last week when he lost to Dominic Thiem in the quarter-finals of the Madrid Open, but the two men suffered contrasting fortunes in Rome on Thursday (AEST).
Seven-time champion Nadal - seeking to reclaim the number-one ranking he conceded last week - hammered Dzumhur 6-1 6-0 after Thiem had gone down in three sets to Fabio Fognini, the Austrian smashing a racquet in anger during an intense contest.
Four of the top eight seeds were eliminated on a busy day of action. Thiem was joined in making an early exit by Dimitrov and John Isner, who lost respective close matches to Kei Nishikori and Albert Ramos-Vinolas, while Kevin Anderson retired after losing the first set to Aljaz Bedene.
Next up for Ramos-Vinolas is a meeting with Novak Djokovic, who eased past Nikoloz Basilashvili 6-4 6-2. Djokovic has not dropped a set in five previous meetings between the pair.
Defending champion Alexander Zverev continued his excellent form with a 7-5 6-2 win over Matteo Berrettini, his 10th victory in a row.