Having made the semi-finals for the third consecutive time, this was a logical progression for the 24-year-old Austrian, who prevailed 7-5, 7-6, 6-1 against the world No 72, this year's surprise package at Roland Garros.
"Del Potro has achieved great victories this year", said Nadal who dropped his first set at Roland Garros in three years in his quarter-final victory over Diego Schwartzman.
Nadal takes a 10-0 French Open semifinal record into his matchup against 2009 U.S. Open champion del Potro.
"It was not a very nice feeling", Thiem told the Court Philippe Chatrier crowd afterward.
"It's very important to regenerate, have a good breakfast tomorrow".
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Yet Thiem's recovery was exceptional, moving out of sight with a ruthless second break and a confident hold to wrap up the opener.
The first set was a tight affair, with Thiem claiming the decisive break in the 11th game but the Italian retained his composure to send the second to a tie-break.
The battle wore on and on, before, on the Austrian's fifth set point, Cecchinato went long to fall two sets behind.
Cecchinato, whose use of the dropshot was often devastating, forced three set points in a tiebreak which became nearly as epic as that against the Serb.
Thiem had to weather three set points for Cecchinato, at 7-6, 9-8 and 10-9. The third set was dominated by Thiem, who raced to a 4-0, two-break lead in 12 minutes. The previous match up saw the Spaniard beat Del Potro in straight sets in the opening round in 2007.
In 2016, Cecchinato was accused of match-fixing but an 18-month suspension was thrown out on a technicality.