The Argentine overcame a sluggish start to defeat Filip Krajinovic 6-4 6-2 and reach the quarter-finals of the Miami Open.
The 29-year-old’s winning run has been extended to 14 matches and a meeting with Milos Raonic, who dismissed Jeremy Chardy 6-3 6-4, awaits on Wednesday.
Del Potro encountered the Canadian in Indian Wells earlier this month and was a convincing 6-2 6-3 victor.
The tournament-favourite lacked intensity in the early stages and his Serbian opponent gleefully capitalised. Del Potro was missing a spark, and while he meandered around the court, the busy Krajinovic establlished a 4-1 advantage.
The underdog adapted quicker to the windy conditions, however his rival soon settled and began crunching forehands. A questionable backhand dropshot attempt from Krajinovic enabled the Argentine to recover the deficit.
Del Potro had established baseline control, and his rival did not possess the attacking arsenal required to knock him off his stride. From 4-1 down, the Indian Wells champion won five games in succession to bank the opening set.
The one-way traffic continued in the second set. A further four games went the way of del Potro before Krajinovic was able to get his side of the scoreboard ticking over again.
The contest lost its edge in the second set, and the No.5 seed cruised into the last eight to continue his unbeaten March.
Earlier in the day, John Isner took out Marin Cilic 7-6(0) 6-3 to net his first Top 5 win in 10 months.
It’s been a disappointing start to the campaign for the big-serving local, but his upturn in form will see him become the American No.1 again next week.
The 32-year-old will take on Hyeon Chung in the quarter-finals. The South Korean, who is yet to drop a set in the tournament, brushed Joao Sousa aside 6-4 6-3.
Borna Coric's excellent month continued with a fine 7-6(2) 4-6 6-4 victory over Denis Shapovalov. The Croatian will take on Alexander Zverev in the last eight after the German won an entertaining late-night duel with Nick Kyrgios 6-4 6-4.
It was a hectic afternoon for Frances Tiafoe, who was on double-duty.
The American completed his match with Tomas Berdych – winning a third set tiebreak – before taking on Kevin Anderson in the last sixteen.
The big-serving South African prevailed against with his youthful opponent though, and will face Pablo Carreno Busta for a place in the semi-finals.