Tsitsipas was riding on the crest of the wave at the Barcelona Open last week, beating the likes of Dominic Thiem en route to a maiden final before world number one Nadal subjected him to a 6-2 6-1 hammering.
The 19-year-old from Greece vowed to learn from a brutal lesson dished out by Nadal on Sunday and overcame Andujar 7-6 (7-2) 6-3 two days later.
Tsitsipas won 71 per cent of points on his first serve, breaking twice in the second set to advance after bossing a first-set tie-break and will now face top seed Kevin Anderson.
Joao Sousa finally claimed a victory at the fourth attempt in the tournament in his homeland, beating eighth seed Daniil Medvedev 7-6 (7-1) 7-5.
Albert Ramos-Vinolas was another seed to crash out, going down 6-2 6-4 to Federico Delbonis, while Cameron Norrie sent sixth seed Robin Haase packing and Nicolas Jarry ousted Leonardo Mayer.
Cecchinato beat John Millman in the Hungarian Open final as a lucky loser last weekend and maintained his momentum with a 5-7 6-3 6-2 success over fellow Italian and fifth seed Fabio Fognini.
Gael Monfils also bowed out in Munich, Mirza Basic defeating the seventh seed 6-2 3-6 6-3, but Philipp Kohlschreiber got past Ivo Karlovic 7-5 6-4 in his homeland.
Yuichi Sugita was another seed to make an early exit, the 119-ranked Yannick Maden coming from behind to win 4-6 7-6 (11-9) 6-2.
Millman missed out on a maiden ATP title when he was beaten by Cecchinato in Budapest and fell at the first hurdle in the Istanbul Open, Dusan Lajovic beating the Australian 6-4 6-0.
Malek Jaziri will face defending champion Marin Cilic in round two in the Turkish city after dispatching fellow Turk Marsel Ilhan 6-1 6-2 and seventh seed Jiri Vesely breezed through at the expense of Daniel Gimeno Traver.
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