The chance of a maiden Grand Slam title has also escaped Cobolli for another few months after his capitulation against Blockx.
Having edged the first set on a tie-break, the Italian lost his way and after surrendering the third set to love in just 20 minutes, could not recover.
“I think my energy was a little bit lower than the other days,” he said. “I feel a little bit more tight and maybe more tired.”
Cobolli admitted Blockx deserved the win and would support him in the next round.
“Alex is very good guy outside the court. He deserved to win, and he won,” he added.
Defeats for Cobolli and Fritz mean that apart from top seed Alexander Zverev, only two top-20 players remain in the top half of the draw in 14th seed Learner Tien and 17th seed Jakub Mensik – and they play one another on Friday.
It means Zverev could feasibly reach the final without playing a top-10 player and will not have to face anyone in the top 20 before the semis.
In the men’s doubles, British pair Arthur Fery and Joshua Paris progressed with a 6-4 5-7 6-4 win over Anirudh Chandrasekar of India and Ivan Liutarevich of Belarus.
Britain’s Neal Skupski and American partner Christian Harrison, the fifth seeds, also advanced as they beat French duo Arthur Reymond and Luca Sanchez 6-0 7-6 (7-3).
But there was disappointment for David Stevenson and Marcus Willis as they lost 5-7 7-6 (7-2) 6-3 to France’s 11th seeds Sadio Doumbia and Fabien Reboul.
